Sarcomas are rare, heterogenous, and often difficult to classify. A large proportion of sarcomas are associated with specific molecular genetic lesions such as translocations, mutations, and amplifications, which are helpful in the diagnosis of individual cases. However, the exact impact of molecular genetics on the final diagnosis of sarcomas is unknown. In this study, all soft tissue and visceral sarcomas arising in patients living in 3 European regions in 2 countries (representing 13 million inhabitants) were collected and reviewed during 2 consecutive years. A molecular analysis was performed for all suspicions of sarcomas with specific genetic lesions [mutations of KIT/PDGFRA in gastrointestinal stromal tumors (GISTs), reciprocal translocation, or amplification of MDM2 in atypical lipomatous tumors, well-differentiated liposarcoma-dedifferentiated liposarcoma (ALT/WDLPS-DDLPS)]. To evaluate the impact of molecular tests, a premolecular analysis diagnosis was proposed with 3 categories of certainty: certain, probable, or possible. A molecular analysis was performed in 763/1484 tumors corresponding to 295 cases in which GIST was suspected, 248 sarcomas with a suspicion of translocation, and 220 cases in which ALT/WDLPS-DDLPS was suspected. Molecular analysis was found to be useful (confirms a probable diagnosis) in 11 (4%) GISTs, 62 (26%) suspicions of translocation, and 66 (31%) suspicions of ALT/WDLPS-DDLPS; and necessary (allows a possible diagnosis) in 2 (<1%) GISTs, 31 (12%) suspicions of translocation, and 19 (9%) suspicions of ALT/WDLPS-DDLPS. This study performed in an epidemiological setting demonstrates the significant impact of molecular analysis on the final sarcoma diagnosis and favors such an analysis on any tumor with a suspicion of a specific genomic abnormality and for which the diagnosis is uncertain.