Yes and no - in clue you play against each other moving around a board and making guesses at person-place-weapon in an attempt to solve the crime first. Information is kept secret and you have to be in the right place and the right time. In Mysterium you win or lose as a team. For the first, longest part of the game, you are each trying to figure out a person-place-weapon assigned just to you (each person has been assigned their own unique person-place-weapon combo). There is no board to move around, no race to the finish - you simply need to all guess your combos before the night ends. The ghost hands out 1-7 cards with dream like pictures (think Dixit, but more complex and darker theme) to each player - this is the player's "dream"/"vision" - each player has 1-7 cards each turn that relate only to what *they* are trying to figure out that turn (first turn everyone is trying to figure out who their person is, when they solve that they move on to place and then to weapon). The cards are public and everyone may advise each other on what person-place-weapon they think any given "dream" is suggesting. After 7 turns (or sooner if everyone has guessed their combos), one of the player combos becomes THE combo - the true murder in the true location with the actual weapon. All the combos are laid out on the table and the ghost gives out one shared dream of 3 cards - one for the person, one for the place, one for the weapon (it's a little more complex...) - the players each vote on which their unique combos the ghost is trying to say is the TRUE one. If the majority guesses right, everyone wins. If not, everyone loses. So, as you can see, Clue may be the closest comparison, but it is not all that similar to Clue.

How similar is this to Letters from Whitechapel? The gameplay sounds very similar - I'm wondering if they are different enough to warrant owning both

Absolutely worth owning both. The gameplay mechanics and reasoning behind them are quite different. Whitechapel is about DEDUCTIVE reasoning based on Jack's hidden movement and trail. Players triangulate where the Jack player is based on where he has been. Sometimes there is only one solution. Pure logic. Mysterium's gameplay is all about INDUCTIVE reasoning. There can be more than one possible solution and gameplay is about getting inside another player's head to understand the solution they chose. Both Fabulous games. Mysterium is more accessible and family friendly. Non-gamers can get into it right away, while Whitechapel is more demanding. Whitechapel is more similar to Fury of Dracula, another great game that has just been republished.

Is the game worth getting if you usually only have 2 players? Our game nights with friends are infrequent. Is it worth it?

Depends on the players, personally I think it makes a great 2 player game.With that said, the game is really meant for 4-5 people. The rule book has special rule changes for more players (where you get to bet on other people being right/wrong), and for fewer people where every person plays two characters at once and some extra cards get added towards the end. It feels a bit duct-taped but the core mechanic of solving whodunits via impressionistic paintings is still fun.

What is the replayability of this game? Will people end up developing a "code" for the pre-existing pictures for the same set of possible murder?

Having played this game (for the first time just yesterday), I really don't think that people will develop a "code". Kind of like Dixit, it is pretty free association for the images. Since the what, where, and who are random with a number of combinations and there are quite a few pictures, it will be very difficult to line up patterns all that much. I found it was pretty hard, in most cases, for the "ghost" to pick a good picture, so most of the selections were quite "out there". A lot of free association and using what other players were selecting to reduce the number of choices, it was a bit more possible to narrow things down.I believe that this will be a very replayable game but I also expect that after a few games, the players will get better at both picking pictures to associate and figuring out what the picture might mean, but not so much because of the selection of pictures but more because the thinking processes for both the ghost and the players will become more refine through learning how to pick.Overall, I find it to be a pretty good game.DaveBoardgames4us

CPSIA Cautionary Statement	Choking Hazard - Small Parts
Item Weight	2.2 Pounds
Number of Items	1
Item Dimensions L x W	11.22"L x 11.22"W
Unit Count	7.0 Count
Material Type	Paper
Are Batteries Required	No
Color	Multi
Theme	Mystery

Mysterium Board Game - Enigmatic Cooperative Mystery Game with Ghostly Intrigue, Family Fun for Kids & Adults, Ages 10+, 2-7 Players, 42 Minute Playtime

Description

Specifications

Common Questions