Parakeratosis is relatively common in both benign and malignant skin diseases. It is a useful feature for classifying certain types of dermatitis; however, its value in distinguishing benign from malignant neoplastic squamous lesions has not been investigated. Parakeratotic nuclei are pyknotic and often elongated, regardless of the underlying disease. However, we have noticed a quite consistent difference in nuclear morphology between benign and malignant parakeratosis, which has not been formally described in the literature. To test the hypothesis that morphological differences may aid in the discrimination between certain benign and malignant dermatopathological lesions, we used computer-aided nuclear morphometry to analyze parakeratosis from 28 cases of squamous cell carcinoma, 19 cases of verruca vulgaris, and 23 cases of psoriasiform dermatitis. Significant differences in nuclear area and area variability were observed between benign and malignant cases. These two parameters together could separate most squamous cell carcinomas from benign cases. Through this study, we hope to raise the awareness that even parakeratosis, the most superficial morphological datum available for histopathological evaluation, may harbor distinct changes of nuclear atypia in squamous cell carcinoma. In some overly superficial shave biopsies, parakeratosis may be the only material available for evaluation. For such cases, if squamous cell carcinoma is in the differential diagnosis, then the parakeratotic nuclei should be examined carefully to determine the likelihood of malignancy. Computer-aided nuclear morphometry may have potential diagnostic value for such cases.