We report on a patient with a disseminated form of porokeratosis in whom bowenoid lesions and squamous cell carcinoma developed in an apparent sequential progression. Local and disseminated metastases ensued, resulting in the death of the patient. Furthermore, we found an overexpression of the p53 protein in the keratinocytes beneath and adjacent to the cornoid lamella in the porokeratotic lesion and throughout the epidermis in a bowenoid lesion. Although malignancy has been reported previously in various types of porokeratosis, the development of fatal metastatic squamous cell carcinoma in the setting of this disease is a rare event. The histopathologic findings of this case document the association of porokeratotic lesions with bowenoid dysplasia and aggressive squamous cell carcinoma and confirm that a p53 functional aberration can be important in a malignant outcome such as this.