The 120 kDa proliferating-cell nucleolar antigen described by Freeman et al. (Cancer Res. 48:1244; 1988) is the most cancer specific of the proliferation-associated nucleolar proteins identified thus far. It is localized in a novel nucleolar microfibrillar structure recently described by Ochs et al. (Cancer Res. 48:6523; 1988). The amino acid sequence has been determined by a combination of cDNA and genomic DNA sequences. This molecule contains, consecutively, four major domains: a basic domain, an acidic domain, a hydrophobic and methionine-rich domain, and a domain rich in cysteine and proline residues. The isolated cDNA was shown to code for the HeLa P120 protein as shown by a similarity in immunoreactivity, mobility on sodium dodecylsulfate-polyacrylamide gel electrophoresis, and patterns of partial digestion of the Escherichia coli-expressed P120 and the HeLa nucleolar P120 protein. This protein is of special interest because it is expressed in early G1 and, in studies to date, it has not been detected in benign tumors and most normal resting tissues.