BACKGROUND. Lobular neoplasia (LN), also known as lobular carcinoma in situ, is an incidental histologic finding in tissue removed at breast surgery. Patients with LN are known to be predisposed to develop invasive or intraductal carcinoma (CAI. This study investigates factors that influence the cancer risk in LN patients. METHODS. Analysis of data concerning long term follow-up (median: 18 yrs) of 236 patients with LN identified in a pathologic review of more than 2000 biopsy specimens with benign epithelial proliferative breast disease. RESULTS. The probability of CA developing in either breast in long term survivors after a biopsy that contained LN was approximately 1/3, which is 5.4 times (95% (;I: 4.2-7.0) the rate in the general population. The relative risk (RK) tended to decrease with increasing age at diagnosis, but was approximately doubled (RR: 1.8; 95% CI: 1.1-3.2) for patients with benign epithelial breast disease preceding their initial diagnosis of LN. CA risk remained markedly elevated for at least 20 years, and increased substantially if there was a second operation showing LNfrom 4.9 (95% CI: 3.7-6.4) after a single operation with LN to 16.1 (95% CI: 6.9-31.8) after a second such operation. CONCLUSIONS. LN is a marker of increased CA risk that is further exacerbated by episodes of preexisting benign breast epithelial proliferative changes, and that remains substantially elevated for many years.