Atypical fibroxanthoma can mimic other tumors, particularly spindle cell squamous cell carcinoma and spindle cell or desmoplastic melanoma. We describe a patient with chronic lymphocytic leukemia who developed acantholytic squamous cell carcinoma on the face, which recurred and metastasized to a cervical lymph node. This tumor was at first diagnosed as atypical fibroxanthoma because of its histologic and immunostaining similarity. It showed weak or negative keratin cocktail staining and strong vimentin staining. However, a recurrent tumor was immunostained for high-molecular-weight keratin and showed strong positivity. Aggressive behavior of this squamous cell carcinoma may be due to altered immune response secondary to chronic lymphocytic leukemia.