A group of patients with paraneoplastic cerebellar degeneration (PCD) have shown to produce auto-antibody to both neurons and tumor cells (anti-Yo antibody). More than 60% of these patients have shown neurological symptoms and anti-Yo antibody production before the underlying cancers were found, which suggests that the test for anti-Yo antibody is important for the early detection and treatment of cancer. Originally, anti-Yo antibody has been characterized as 1)labelling the cytoplasm of cerebellar Purkinje cells immunohistochemically, 2)binding to the 62 and 34kDa bands on immunoblots of Purkinje cell extracts, 3) being present in female patients with gynecological or breast cancers. Recently, the common binding-epitope of anti-Yo antibody has been reported as leucine-zipper protein. In order to detect the anti-Yo antibody precisely, we examined the immunohistochemical and western blot characters of the recombinant leucine-zipper protein- reactive (anti-Yo) antibody. The results were, 1)sera containing leucine- zipper protein-reactive antibody labels both cerebellar Purkinje cells but some sera might contain other antibodies together with anti-Yo that confuse the immunostaining character of anti-Yo antibody, 2)the antibody binds to 58 kDa band and sometimes co-binds to 34kDa on immunoblots of cerebellar tissue extracts. The underlying cancers are mainly adenocarcinoma in the ovary, fallopian tube, uterus, or breast but occasionally large cell lung and bile duct cancers have been found. Interestingly, a male patient had an antibody similar in character to be anti-Yo antibody immunohistochemically and on immunoblots, that did not recognize leucine-zipper protein and the underlying carcinoma was small cell lung cancer. These results suggest that 1) the diagnosis of anti-Yo antibody should be based on the antibody's reactivity with leucine-zipper protein, 2) some sera with the anti-Yo antibody label other tissues besides the Purkinje cell cytoplasm because of the co-existance of other antibodies seen immunohistochemically and on immunoblots, 3) the search for underlying cancers should not be limited to gynecological or breast carcinomas.