Keratoacanthoma (KA) is a comparatively common low-grade tumor that initiates in the pilo-sebaceous glands and pathologically mimics squamous cell carcinoma (SCC). Essentially, strong debates confirm classifying keratoacanthoma as a variant of invasive SCC. The clinical behavior of KA is hardly predictable and the differential diagnosis of keratoacanthoma and other conditions with keratoacanthoma-like pseudocarcinomatous epithelial hyperplasia is challenging, both clinically and histopathologically. This article aims to illustrate and explicate some of these complicated issues by presenting two cases of KA and a relevant review of literature. It also targets the clinical, histopathologic, and immuno-histochemical features of these two cases.Both presented lesions of this study had appeared on the vermilion border of the lower lip and no vascular or perineural invasion was observed. The results of the immuno-histochemical survey, particularly in staining with marker CD30, confirmed the differential diagnosis of keratoacanthoma from keratoacanthoma-like pseudocarcinomatous proliferations which was consequent to the CD30+ lymphoid infiltration.Histopathological and immunohistochemical investigation is necessary to disprove the invasive biologic behavior of keratoacanthoma and also to refute all conditions with keratoacanthoma-like pseudocarcinomatous epithelial hyperplasia.Key Words: Immunohistochemistry; Keratoacanthoma; KA; CD30