About half of the patients with paraneoplastic diseases develop an immune response against neuronal antigens expressed by both the tumor and the nervous system. In 31 patients with anti-Hu antibodies and 19 patients with anti-Yo antibodies, we searched for the presence of additional non-neuronal auto-antibodies and further studied whether the presence of such auto-antibodies was correlated with a specific oncological or neurological presentation. Positive antinuclear antibodies (ANA) were found at a titer of 1:40 or above in 48% patients with anti-Hu antibodies, and in 37% patients with anti-Yo antibodies. Anti-cytoplasmic antibodies were also detected in 42% patients with anti-Yo antibodies. No specific correlation between the presence of non-neuronal auto-antibodies and clinical characteristics of the patients could be identified. In particular, neither the type of underlying cancer, the overall survival, the tumor response to treatment, nor the neurological presentation were related to the serological status.