A 62-year-old male was referred for management of oral squamous cell carcinoma (OSCC), previously diagnosed in another service. The patient complained of persistent oral discomfort for 10 months, reported being a social drinker, and denied smoking. Intraoral examination revealed a vegetating, hardened lesion, measuring 3.0 cm, in transition between the retromolar trigone, soft palate, and buccal mucosa. Microscopic examination of the incisional biopsy performed previously revealed malignant epithelial cells proliferate and invade the surrounding stroma as islands and cords of epithelial cells, with the presence of cystic spaces and clear cells, resembling mucoepidermoid carcinoma (MEC). The histological findings led to a diagnosis of MEC or OSCC. Based on the correlation between the morphological, immunohistochemical, and histochemical findings, the diagnosis of OSCC with cystic spaces and clear cells was supported. The patient was referred for further therapeutic intervention. Recognizing the histological variants of OSCC is important, due to the similarity with other neoplasms.