Background <p>The historical standard for axillary management after occult malignancy identified at the time of contralateral prophylactic mastectomy is axillary lymph node dissection (ALND). However, the optimal strategy for managing the axilla in patients undergoing contralateral prophylactic mastectomy is unknown. Herein, we evaluate the cost effectiveness of the possible strategies.</p> Methods <p>A decision tree was constructed with event probabilities from a literature review. Cost data were obtained from the Nationwide Ambulatory Surgery Sample. A cost-effectiveness analysis was conducted to determine expected costs, number of sentinel lymph node (SLN) surgeries in the absence of occult malignancy, number of ALND avoided, and incremental cost-effectiveness ratios for each of the approaches.</p> Results <p>Routine SLN surgery increased costs by $US12,151.90 and resulted in 985 unnecessary SLN surgeries per 1000 patients but no diagnostic ALND. Preoperative magnetic resonance imaging increased costs by $2065.26, required no unnecessary SLN surgeries, and a rare need for ALND. Routine SLN mapping for delayed SLN surgery increased costs by $269.22 and required no unnecessary SLN surgeries or diagnostic ALND.</p> Conclusions <p>Difference in cost (excluding routine SLN surgery) was only a small proportion of the overall cost, whereas there was a wide range in excess SLN surgeries and ALND. Thus, cost should not be a primary driver of decision-making in this scenario. It is therefore important to focus on the relative risks of excess SLN surgery and diagnostic ALND, which are minimized by routine SLN mapping for delayed SLN surgery and preoperative magnetic resonance imaging.</p>