Abstract Introduction The management of Intraductal papillomas (IP) of the breast diagnosed on core needle biopsy (CNBx) is still controversial. For IP with atypia, excision is generally recommended. For IP w/o atypia, data for excision vs. observation are variable. A clearer understanding of the risk of the presence of invasive or in situ malignancy (IDC or DCIS) coincident with IP, as well as the long-term risk for cancer would be helpful in managing these patients. The aim of this study is to evaluate the rate of malignancy on immediate excision or with prolonged follow-up. We hypothesized that IP w/o atypia do not require excision, as the risk of malignancy is low. Conversely, we hypothesized that IP w/ atypia should be excised because of a significant rate of concomitant malignancy. We also evaluated the long-term risk of malignancy in either breast with excision or observation of women with IP. Methods 266 women who underwent a CNbx between 1995 and 2010 were identified from surgical pathology and breast imaging records. Four groups were defined based on the CNBx diagnosis (IP w/o atypia, IP with atypia, IP + ADH/ALH and Papillomatosis) and were also separated on the basis of immediate excision versus observation. For the 15-year period, it was generally the policy to excise IP lesions with atypia or ADH/ALH. Management of IP w/o atypia was more variable, but in the most recent 5 years, patients with IP w/o atypia were usually observed. For those who underwent immediate excision, the proportions with IDC or DCIS were calculated and compared using Fisher's exact test. Kaplan Meier curves were determined for each group's estimated time to cancer diagnosis, and significance was evaluated by the log-rank test. Results When surgical excision was performed for IP w/ atypia or IP + ADH/ALH on CNBx, cancer was found in 32% and 38.5% respectively. Of the 109 excisions for IP w/o atypia, cancer was found in 8.3%, significantly different from IP w/ atypia (p=0.004) and IP + ADH/ALH (p=0.007). For patients without atypia or ADH/ALH at the time of biopsy and no cancer on excision, the probability of remaining cancer-free was not significantly different for patients who had immediate surgical excision versus those that were observed (93.8% and 91.5% cancer-free at 10 years, p= 0.773). For patients with atypia or ADH/ALH at the time of biopsy but no cancer on excision, the probability of remaining cancer-free in both breasts was 85.9% at 10 years, and did not differ between patients who were excised or observed (p= 0.518). However, those w/atypia or ADH/ALH were significantly less likely to remain cancer-free than those w/o atypia (85.9% versus 92.8% at 10 years, respectively, p=0.008). Conclusions After a CNBx showing IP w/ atypia or IP + ADH/ALH, surgical excision is clearly justified, based on a 30-40% risk of concomitant invasive or in situ cancer. For IP w/o atypia, the likelihood of cancer is much lower. Moreover, even with excision, the finding of IP with atypia carries a significant risk of developing cancer long-term, and such patients should be followed carefully and perhaps should be considered for chemoprevention. Citation Format: Khan S, Diaz A, Archer KJ, Lehman RR, Mullins TC, Cardenosa G, Bear HD. Intraductal papillomas: Risk of cancer, immediate and delayed. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-37.