Melanoma which is extensively locally recurrent or metastatic to the skin is often unsuitable for or resistant to surgery, radiation therapy or regional or systemic chemotherapy. Diphencyprone (DPCP) is a potent contact sensitizer which is used in the treatment of cutaneous warts. We use DPCP in an aqueous cream base, applied topically by the patients once per week, to treat extensive cutaneous metastatic melanoma. For each patient, the concentration of DPCP is titrated to produce a brisk but tolerable contact hypersensitivity response at treated sites. Of 33 patients who have so far completed at least 2 months of DPCP treatment, 55% achieved complete clearance of often widespread skin metastases, and 4 patients were also noted to have regression of metastatically involved lymph nodes. One patient displayed complete regression of all metastases in his skin, inguinal nodes and lungs. An additional 33% of patients showed partial response to DPCP, with either regression of some but not all skin lesions, or substantial slowing of the rate of disease progression. Hence 88% of treated patients have shown at least partial response to this inexpensive and relatively non-invasive treatment, with some patients also showing bystander immune mediated regression of metastases. Topical immunotherapy with DPCP should be considered for extensive cutaneous metastases unsuitable for other therapies.