BACKGROUND: There is increasing interest in establishing diagnostic and treatment guidelines for high-risk squamous cell carcinoma (SCC). Single-cell SCC has been recognized as a high-risk subtype but continues to be a less commonly reported and more poorly understood variant.

OBJECTIVE: To present the current literature on single-cell SCC.

MATERIALS AND METHODS: A review of the literature on single-cell squamous cell carcinoma.

RESULTS: There are fewer than 100 cases of single-cell SCC in the literature. The reporting studies demonstrate an increase in the risk of metastasis compared with non-single-cell tumors. Confounding variables reported include other coexisting high-risk features: diameter > 2 cm, depth > 6 mm, and difficulty detecting single tumor cells. It is therefore unclear whether single-cell SCC is an independent risk factor for recurrence and regional spread. Studies have described use of immunostaining as a means to improve tumor detection.

CONCLUSION: Single-cell SCC continues to be an underreported SCC variant. Given its apparent aggressive behavior, more studies are warranted to better understand its tumor biology and behavior and to improve patient outcomes. Based on our present knowledge, complete tumor excision with or without the aid of immunostaining and use of multidisciplinary care are recommended.