BACKGROUND:High-risk patients undergoing prophylactic mastectomy (PM) may have unsuspected cancers identified on pathology. The optimum way to identify and manage them is controversial. Magnetic resonance imaging (MRI) may identify occult cancer preoperatively. Sentinel lymph node biopsy (SLNB) allows intraoperative staging and axillary dissection during the same operation. We determined the efficacy and cost of MRI and/or SLNB in managing high-risk PM patients. METHODS:We reviewed 192 PMs in 173 patients from 1999 to 2005. Costs were estimated for MRI and SLNB during PM by the 2005 Medicare Resource-Based Relative Value Scale. We also estimated costs and procedures for the four strategies in a larger hypothetical cohort. RESULTS:A total of 19 (10%) of 192 PMs contained occult cancers, 14 ductal carcinoma-in-situ (DCIS) and 5 invasive ductal carcinoma (IDC). In 59 patients, MRI detected an IDC but missed two DCIS and an IDC. Positive MRIs generated an additional average cost of $1,207 per patient. In 56 PMs with SLNB, 6 occult cancers were found, 5 DCIS and 1 IDC, all with negative SLNBs. Adding a SLNB costs an additional average of $644. A theoretical analysis demonstrated that PM alone costs $808 per patient, PM with SLNB costs $1,420, PM with MRI and selective SLNB costs $1,774, and PM with routine MRI and SLNB costs $2,379. CONCLUSIONS:MRI adds great cost and misses most occult cancers in PMs. SLNB allows the rare patient with occult IDC to avoid axillary dissection but adds cost. Given the low rate of unsuspected invasive cancers and the costs of MRI and SLNB, neither is recommended as standard practice for PM patients.