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Purpose: Radioguided localization can assist the surgery of hard-to-find lesions. The aim was to evaluate the results of the 125I Radioactive Seed Localization (RSL) technique to guide a margin-free tumoral resection of mesenchymal tumours compared to conventional surgery and its influence in oncological outcomes. Methods: Retrospective observational study of all consecutive patients who underwent 125I RSL for the surgery of a mesenchymal tumour from January 2012 to January 2020 in a tertiary referral centre in Spain. The control group was formed by patients with conventional surgery in the same period and centre. A Propensity Score matching at 1:4 ratio selected the cases for analysis. Results: A total of 10 lesions excised in 8 radioguided surgeries were compared to 40 lesions excised in 40 conventional surgeries, with equal proportion of histological subtypes in each group. There was a higher proportion of recurrent tumours in the RSL group (80 % [8/10] vs. 27.5 % [11/40]; p: 0.004). An R0 was achieved in 80 % (8/10) of the RSL group and 65 % (26/40) of the conventional surgery group. The R1 rate was 0 % and 15 % (6/40), and the R2 rate was 20 % (2/10 and 8/40) in the RSL group and conventional surgery group, respectively (p: 0.569). No differences were detected in disease-free or overall survival between the different histological subtypes in the subgroup analysis. Conclusion: The 125I RSL technique of a challenging sample of mesenchymal tumours achieved a similar margin-free tumoral resection and oncological outcomes as conventional surgery. [ABSTRACT FROM AUTHOR]