PurposeSquamous cell carcinomas and adenocarcinomas are the most common types of cervical cancer. Compared to squamous cell carcinomas, adenocarcinomas are more common in younger women and have a poorer prognosis. Yet, so far, no useful biomarkers have been developed for these two types of cancer. In the following study, we examined the combination of cytokeratin 5/6, p63, p40 and MUC5AC for distinguishing squamous cell carcinoma (SCC) from adenocarcinoma of the cervix (AEC).Materials and methodsA total of 101 SCC and 108 AEC were collected. Immunohistochemical analyses were conducted to determine the expression of CK5/6, p63, p40, CK7 and MUC5AC. One pathologist who was blinded to the patient’s clinical and pathological data interpreted the staining results.ResultsMUC5AC and CK7 were detected in 81.48 and 82.41% of AEC cases compared to 9.9 and 49.50% of SCC cases (P < 0.05); the specificity of MUC5AC was higher than that of CK7 in AEC (P < 0.05). The sensitivity of MUC5AC combined with p40 or p63 was similar to that of CK7, but the specificity was slightly higher than that of CK7 in AEC. Moreover, the expression of MUC5AC was correlated with the degree of tumor differentiation in adenocarcinomas (P = 0.036) and was not related to the prognosis of cervical adenocarcinoma and subtypes.ConclusionsMUC5AC may be useful as a biomarker for differential diagnoses between squamous carcinoma and adenocarcinoma of the cervix.