The present study evaluated the ability of males with fragile X syndrome (FXS), nonsyndromic autism spectrum disorder (ASD), or typical development to learn new words by using as a cue to the intended referent an emotional reaction indicating a successful (excitement) or unsuccessful (disappointment) search for a novel object. Performance for all groups exceeded chance-levels in both search conditions. In the Successful Search condition, participants with nonsyndromic ASD performed similarly to participants with FXS after controlling for severity of ASD. In the Unsuccessful Search condition, participants with FXS performed significantly worse than participants with nonsyndromic ASD, after controlling for severity of ASD. Predictors of performance in both search conditions differed between the three groups. Theoretical and clinical implications are discussed.