Rationale: Unilateral manifestation of lymphedema during everolimus therapy has been described only rarely, mostly in transplant recipients. Patient concerns: We report the first case of a patient who developed unilateral abdominal lymphedema, during a short period of everolimus treatment for renal cancer. Diagnosis: The abdominal asymmetry occurred only on the right side of the abdomen, neither ultrasound nor CT scan detected ascites but showed enlargement of the abdominal wall. The Naranjo Adverse Drug Reaction Probability scale was evaluated, in this case, a score of 6 indicated a probable adverse reaction to everolimus. Interventions: Discontinuation of everolimus therapy led to immediate alleviation and reduction of the lymphedema, with worsening once again after initiating retreatment with everolimus at a reduced dose. Outcomes: The patient's lymphedema recovered after discontinuation of everolimus. Lessons: This rare case demonstrates the importance of the selection of mammalian target of rapamycin inhibitors using caution, especially for patients with a high risk of developing lymphedema.