Oral squamous cell carcinoma with prominent clear cell differentiation is a rare occurrence. A 35-year-old female patient presented with a nonhealing ulcer persistent for 1-month involving the left lateral border of the tongue and lingual vestibule. Lobules of malignant squamous epithelial cells with abundant cytoplasm and vesicular nuclei in the connective tissue were observed following histopathology. Neoplastic cells constituting majority of lobules exhibited clear cell changes. Periodic acid-Schiff and mucicarmine stains showed negative reaction. Immunohistochemical study using antibody for cytokeratin, revealed diffuse and intense positivity. The neoplastic cells showed complete negative reaction with antibodies for vimentin, smooth muscle actin and homatropine bromide-45 antigens.