Keratoacanthomas are distinct skin lesions that occur most often as solitary tumors in sun-exposed areas in elderly, fair-skinned patients. Clinically, these tumors are characterized by a rapid onset and regression within months. Keratoacanthomas display distinct histological features including a keratin-filled crater lined by a proliferating squamous epithelium. Cytologically, there may be overlap with classical well differentiated squamous cell carcinoma. Rarely, otherwise typical keratoacanthomas show intravascular and perineural invasion and lymph node metastases. Keratoacanthomas should, therefore, be considered to be a clinically distinct variant of well differentiated squamous cell carcinoma capable of spontaneous regression. This view is supported by their common etiology, occasional concurrent occurrence, and a multitude of studies revealing no substantial differences between these two lesions. Regression is immunologically mediated and activated by a variety of molecular mechanisms. Considering the common nature of keratoacanthomas and well differentiated squamous cell carcinomas, and the lack of any features predicting prognosis, surgical excision of keratoacanthoma is advisable.