The occurrence of an aggressive papillary middle ear/temporal bone tumor (APMET) and a benign adnexal papillary tumor of probable mesonephric origin (APMO) in a patient with von Hippel-Lindau disease (VHL) is reported. Histologically, both tumors were identical to papillary cystadenomas of the epididymis and broad ligament of probable mesonephric derivation. A comprehensive literature review showed that including the current case, seven of 46 (15%) documented cases of APMET and four of four (100%) cases of APMO arose in patients with VHL. Given an estimated minimum birth incidence of 1/36,000, a one-sample test of binomial proportion using the exact method establishes that the association of APMET and APMO with VHL is highly significant (p = 1.4 x 10(-24) and 1 x 10(-18), respectively). The data indicate that APMET and APMO may represent major visceral manifestations of VHL. Accordingly, in the presence of one of these tumors strong consideration should be given to the diagnosis of VHL, given either the presence of another major component of VHL or documentation of VHL in at least one consanguineous relative.