Acquired perforating dermatosis (APD) is a very rare disorder which has been described in association with systemic diseases such as diabetes mellitus, HIV infection or lymphoma. In this report we describe a patient with APD associated with sclerosing cholangitis and diabetes mellitus who was successfully treated with rifampicin. A 33-year-old Indian woman with a history of extensive pancreatic surgery, sclerosing cholangitis and insulin dependent diabetes mellitus was referred to our unit with intractable pruritus. She was treated with cholestyramine, ursodeoxycholic acid, several analgesics, UVB therapy, topical steroids, sedative antihistamines and plasmapheresis without significant improvement. Increasingly severe itching was associated with papular skin changes limited initially to the lower limbs but which later involved her entire body. Biopsy of a representative lesion showed the changes of APD. She was subsequently treated with rifampicin which produced a dramatic resolution of pruritus within 3 weeks and the skin changes progressively resolved over subsequent months. In this newly described association of APD with sclerosing cholangitis, rifampicin treatment appeared to be efficient in ameliorating pruritus and the papular skin changes typical of APD.