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The aim of the study was to analyze the medical and economic interest of OSNA molecular technique, compared to conventional postoperative histopathologic evaluation for sentinel lymph node exploration in breast cancer patients. This retrospective cost-benefit study was conducted in the French Universitary Hospital of Saint Etienne on patients who received sentinel lymph node exploration between July 1, 2007 and December 31, 2009. Lymph nodes were analyzed by conventional postoperative histological evaluation in group 1 (82 patients) and OSNA in group 2 (86 patients). Costs were analyzed in three different ways: surgery cost, hospitalization cost and histopathologic cost. Average operating time was slightly shorter for group 1 (histology) [71.9 vs. 76.8 min for group 2 (OSNA)]. Time and operating costs were not significantly different (p = 0.293). The average cost of pathological examination was significantly higher in group 2 (35.04 euros per node in group 1 vs. 291.84 euros per node in group 2 p < 10(-3)). The average length of hospital stay was significantly longer in group 1 (5.4 days in group 1 vs. 4.2 days in group 2, p = 0.0065). The total costs were not significantly different between both groups (3,774.6 euros in group 1 vs. 3,393.9 euros in group 2 p = 0.055). The sentinel lymph node analysis with OSNA technique does not lead to higher expenses. It also avoids another surgery for 20% of patients. A prospective multicentric medico-economic study made with a larger effective would probably confirm these results.