Seroma is the most common complication of mastectomy. The aim of this systematic review is to clarify the pathophysiology of seroma.A computer-assisted MEDLINE search was conducted, and additional references were found in the bibliographies of these articles. The reference terms ''breast cancer'', ''mastectomy'', ''seroma'', ''lymphocele'' and ''lymphocyst'' were used as both keyword and subject terms. The search was limited to studies published in English.The definition of seroma was highly variable across studies, but was most commonly a seroma large enough to be noticed by the patient or medical staff and affecting the patient's satisfaction in the immediate or acute postoperative period. So far, only limited data are available on the severity of seroma. With respect to the pathophysiology of seroma, the data indicated that several anatomical factors, especially dead space, likely contribute to seroma formation. However, it was obscure whether seroma was due to lymph-like fluid or exudate.There is considerable variability in the way seroma is defined across studies, and its pathophysiology remains uncertain.