Nine pineal parenchymal tumors were studied by comparative genomic hybridization. These consisted of three pineocytomas (WHO grade II), three pineal parenchymal tumors of intermediate differentiation (WHO grade III), and three pineoblastomas (WHO grade IV). An average of 0 chromosomal changes per pineocytoma, 5.3 per pineal parenchymal tumor of intermediate differentiation (3.3 gains vs. 2.0 losses), and 5.6 per pineoblastoma (2.3 gains vs. 3.3 losses) were found. The most frequent DNA copy number changes among pineal parenchymal tumors of intermediate differentiation and pineoblastomas were gains of 12q (3/6 cases), 4q, 5p, and 5q (2/6 cases each), as well as losses of 22 (4/6 cases), 9q, and 16q (2/6 cases each). Among pineal parenchymal tumors of intermediate differentiation, the most common chromosomal imbalances were +4q, +12q, and -22 (2/3 cases each), and in pineoblastomas -22 (2/3 cases). Five high level gains were identified, all of them in pineoblastomas; these were found on 1q12-qter, 5p13.2-14, 5q21-qter, 6p12-pter, and 14q21-qter. Clinically, all patients with pineocytomas and pineal parenchymal tumors of intermediate differentiation were alive after a mean observation time of 142 and 55 months, respectively, whereas all patients with pineoblastomas had died after an average of 17 months. Our findings suggest that pineal parenchymal tumors of intermediate differentiation are cytogenetically more similar to pineoblastomas and prognostically more similar to pineocytomas. Furthermore, imbalances in higher-grade pineal parenchymal tumors mainly affect gains of 12q and losses of chromosome 22.