Liposarcoma is a malignant tumor of adipocytic differentiation that rarely arises within the mediastinum. Most of the existing data available comes from scattered case reports and a few small series. The World Health Organization (WHO) recognizes four basic types of liposarcoma: well-differentiated/atypical lipomatous tumor (ALT), dedifferentiated, myxoid and pleomorphic liposarcoma (PLS). All of these liposarcoma subtypes have been recorded to occur within the mediastinum. On morphologic grounds liposarcoma can present a challenge for diagnosis as it can be difficult to distinguish from benign adipocytic neoplasms, or in the case of dedifferentiated liposarcoma (DDLS), from virtually any other type of sarcoma. Molecularly the most common subtypes of liposarcoma are characterized by specific, recurrent genetic alterations involving amplification events of MDM2 and CDK4 in well-differentiated liposarcoma (WDL) and a recurrent t(12;16)(q13;p11) in myxoid liposarcoma (MLS). MDM2 and CDK4 amplification can be assessed by immunohistochemistry, fluorescence in situ hybridization, or molecular techniques that evaluate copy number alterations and amplifications such as array based assays and next generation sequencing (NGS). In addition to WDL and MLS, a few additional rare subtypes of liposarcoma may occur in the mediastinum including PLS, myxoid WDL, thymoliposarcoma, and sclerosing high-grade liposarcoma. The present review will focus on the clinicopathologic features of the various histologic types of liposarcoma described in the mediastinum and their differential diagnosis. Data is derived from review of the largest series published in the more recent literature on these tumors.