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The purpose of this review is to present the most recent advances in the diagnosis of the more common leiomyosarcoma (LMS) anatomic variants, potentially useful prognostic markers that have recently been identified and the systemic approaches currently used or under evaluation to improve the outcome of patients with this disease.Over the last few years emphasis has been placed on incorporating effective imaging tools and using pathological biomarkers in the diagnostic workup of LMS. Moreover, efforts are being made to identify meaningful prognostic and predictive parameters that will aid the development of effective novel therapeutics. The number of systemic therapies available to treat LMS has increased over the last decade, but the selection of systemic therapy is not based on the anatomic origin of LMS.Currently, the only curative option in LMS is surgery and despite progress in systemic therapy the outcome of patients with advanced/metastatic disease remains poor. Better understanding of the underlying biology of the LMS variants, improved diagnostics and more effective, less toxic therapeutic agents are required.