It is known that most cases of Ovarian Hyperstimulation Syndrome (OHSS) are associated with the therapies for ovulation induction. However, OHSS may rarely be associated with a spontaneous ovulatory cycle, usually in the case of multiple gestations, hypothyroidism or polycystic ovary syndrome. We report a case of severe OHSS in spontaneous pregnancy with invasive mole in a 34 years old woman. The clinical picture showed abdominal pain, massive ascites, nausea, dyspnea and amenorrhea. After imaging examinations and laboratory tests, the diagnosis was established. The patient was managed expectantly with no complications. Although spontaneous ovarian hyperstimulation is a rare entity, it is important that the physician recognizes this condition. Prompt diagnosis and successful management is likely to avoid serious complications, which may develop rapidly.