221. Which one of these is the odd one out and what's the big deal about it? 室 局 師 胆 手

Answer:

室  SHITSU, muro - room

局  KYOKU - office

師  SHI - teacher, army

胆  TAN - gallbladder, courage

半  HAN, naka(ba) - half

All take 大 (DAI, oo(kii) - big) in front to make a word, but only 室 uses the "Oo" reading (Oo-muro); the others are all "Tai/Dai-": 

大室 Oomuro, 

大局 Taikyoku, 

大師 Daishi, 

大胆 Daitan, 

大半 Taihan.