There are few case reports in the English literature concerning malignant transformation of an epidermal cyst into squamous cell carcinoma. We report a case of squamous cell carcinoma arising from a 40-year epidermal cyst in the proximal left thigh of a 74-year-old man. The epidermal cyst had increased in size in the previous 3 years. The patient presented with a discharge from the lesion. Ultrasonography and magnetic resonance imaging of the lesion suggested malignancy. An intra-operative frozen section of an incisional biopsy of the lesion found it to be an epidermal cyst with suspected malignant change, so a marginal excision of the lesion was performed. Squamous cell carcinoma arising from the epidermal cyst was confirmed histologically. A wide excision was done in order to obtain an adequate resection margin. A computed tomographic scan of the thorax and abdomen found no evidence of metastases. No evidence of recurrence was noted in the latest follow-up, 2 years postoperatively.