Most attempts to elucidate primary cytogenetic events have been made on the basis of chromosome analysis of cells from the later stages of tumor development. Hence it is difficult to decide which, if any, of the observed chromosomal alterations are causative rather than consequential in neoplastic development. One approach to understand the role of chromosomal changes in neoplasia is to examine the chromosomal constitution of cells at early stages in the process of carcinogenesis. We have developed a method for direct preparation of metaphase plates of cells from preneoplastic liver nodules and we present herein the first report of nonrandom chromosome changes in solid tumor precursor cells. The results of the cytogenetic analysis demonstrated trisomies/polysomies for chromosome 11 and chromosome 19. A specific increase in the number of chromosome 19 was found in 43% of the 37 plates karyotyped and 25% of the plates demonstrated increase in the number of chromosome 11. The finding shows that gross chromosomal changes such as polysomies may play an important role in the early development of tumors. They further indicate the presence of a gene on chromosome 19 with an essential role either in the initiation or promotion of the neoplastic transformation of hepatocytes.