Esophageal basaloid squamous cell carcinoma may resemble small cell carcinoma biopsy specimens and cause difficulties in pathology diagnosis. We aimed to clarify the clinicopathological significance of small cell carcinoma-like morphologies in basaloid squamous cell carcinoma. Thirty biopsy specimens of esophageal basaloid squamous cell carcinoma were reviewed and compared with 13 matched surgical specimens. Small cell carcinoma-like features, such as diffuse growth, nuclear molding, or nuclear crush artifact, were identified in 80% (24/30) of the biopsies and in 77% (10/13) of the surgery specimens, but in a proportionally much smaller area in the surgical specimens than in the biopsy samples. The presence of a small cell carcinoma-like feature had no impact on patients´ outcome. Immunohistochemically, synaptophysin and chromogranin A were consistently negative, while CD56 was expressed in 42% (10/24) of basaloid squamous cell carcinomas with small cell carcinoma-like features. p16, a highly sensitive marker for small cell carcinoma, was also expressed in 8% (2/24). p40 was expressed in all cases of basaloid squamous cell carcinoma. In conclusion, small cell carcinoma-like features are frequent and conspicuous in biopsies, which are probably caused by exogenous factors such as friction and external pressure that occur in biopsy procedure and in the tumor environment. Small cell carcinoma-like features may lead to a misinterpretation of a true small cell carcinoma, if CD56 is the only neuroendocrine marker expressed. p16 expression may also be detected in basaloid squamous cell carcinoma.