Soft tissue neoplasms are infrequently encountered by most surgical pathologists. The presence of overlapping histologic features in these tumors, combined with their rarity, can make them a true diagnostic dilemma on histology alone. The purpose of this review is to take one of these common features, the presence of myxoid stroma, and systematically discuss the clinical, radiological, pathologic, and molecular findings that can aid the practicing pathologist in arriving at the correct diagnosis. Two lesions discussed, the cutaneous myxoma and the intramuscular myxoma, are important not only because they are benign and therefore do not need aggressive treatment, but also because both can be associated with underlying genetic syndromes. Myxoid liposarcoma is a translocation sarcoma with monomorphic cells and a tendency to metastasize to soft tissue and bone. Low-grade fibromyxoid sarcoma is a bland lesion that may recur decades after the original diagnosis and treatment, necessitating long-term follow-up. Myxofibrosarcoma is the most pleomorphic tumor of this group and also the tumor that lacks helpful ancillary studies. Overall, this is a heterogeneous group of lesions with distinct features that allow for differentiation in most cases, despite the myxoid stroma common to all.