Some conditions are predisposed to excessive lymphocyte responses, which can progress to a benign condition, ie, atypical cutaneous lymphoid hyperplasia (ACLH), or a malignant lymphoma. Clinical diagnosis of drug-associated pseudolymphoma can be based on a temporal association between drug ingestion and lesion onset followed by resolution without recurrence after discontinuation of drug administration. Herein, we report the case of a 66-year-old man with advanced colon carcinoma with ACLH developed while receiving chemotherapy regimen with oxaliplatin/5-fluorouracil/leucovorin. The authors postulate that chemotherapy can promote an aberrant immune response to an antigen that can be the drug itself or other self-antigens.