We describe the first case of unilateral spiny hyperkeratosis (SH) of the left hand, review the literature and discuss possible patho- mechanisms. SH can be sporadic or familial, often appearing in healthy individuals. However, there is an association with various malignancies in a significant number of the sporadic cases. Although there is no satisfactory explanation of this association, we agree with previous authors that a patient with SH appearing in adult life should be evaluated and followed for the presence of malignancy. Other patients with SH may suffer from a variety of nonmalignant diseases, which may be coincidental or causally related. SH is not a premalignant lesion of the skin and should not be confused with porokeratosis which has a malignant potential. Except for excision of individual lesions, there is no permanent cure.