A 55-year-old man presented with oral mucosal ulcers, blackening of both hands, and hyperpigmentation on axillary, anal, and inguinal regions for the last 3 months, which were all progressive. The patient was referred to the oncology department with the diagnosis of acanthosis nigricans for investigation of an underlying malignancy. He was a smoker. A computed tomography scan of thorax revealed enlarged mediastinal lymphadenopathies and a lesion on the left upper lobe. Fine-needle aspiration biopsy of the mediastinal lesion was consistent with squamous cell carcinoma, and biopsies of the skin and oral mucosal lesion also further confirmed the diagnosis of acanthosis nigricans. After docetaxel and cisplatin chemotherapy, a significant improvement in his skin and mucosal lesions was observed with almost complete resolution of the pulmonary lesion and the mediastinal lymph nodes.