Myospherulosis is a rare tumor caused by interaction of extravasated erythrocytes and exogenous or endogenous lipids. Fifty-nine articles presented 181 patients with myospherulosis since first description in 1969. Myospherulosis seems to occur in any age and in any part of the body; however, most frequent sites are paranasal sinus and subcutaneous tissue. In most cases, exogenous lipids from postoperative packing are damaging the erythrocytes, but also spontaneous cases are described. Diagnosis is made by histology but can be already suggested by radiographic imaging. Differential diagnoses include infections by fungi or algae due to histopathologic similarity. Besides that, radiographic imaging and morphology can wrongly be interpreted as carcinomas, metastases, osteofibrosis, or echinococcosis. Myospherulosis is a benign process, with symptoms deriving from the space occupying character and surgical excision can bring cure. We discuss the clinical presentation, diagnosis, and treatment and provide a systematic review of the literature on myospherulosis.