Serous cystadenoma(SC) is a benign pancreatic cystic tumor. Surgical resection is recommended for symptomatic forms, but laparoscopic fenestration of large symptomatic macrocystic SC was not yet described in the literature. In this study, 3 female patients underwent laparoscopic fenestration for macrocystic SC(12-14 cm). Diagnosis was established via magnetic resonance imaging and endoscopic ultrasound, with intra-cystic dosage of tumors markers(ACE and CA19-9) in 2 patients. All patients were symptomatic and operated on 15-60 mo after diagnosis.Radiological evaluation showed constant cyst growth.Patients were informed about this new surgical modality that can avoid pancreatic resection. The mean operative time was 103 min(70-150 min) with one conversion.The post-operative course was marked by a grade A pancreatic fistula in one patient and was uneventful in the other two. The hospital stay was 3, 10, and 18 d, respectively. The diagnosis of macrocystic SC was histologically-confirmed in all cases. At the last followup(13-26 mo), all patients were symptom-free, and radiological evaluation showed complete disappearance of the cyst. Laparoscopic fenestration, as opposed to resection, should be considered for large symptomatic macrocystic SC, thereby avoiding pancreatic resection morbidity and mortality. Serous cystadenoma (SC) is a benign pancreatic cystic tumor. Surgical resection is recommended for symptomatic forms, but laparoscopic fenestration of large symptomatic macrocystic SC was not yet described in the literature. In this study, 3 female patients underwent laparoscopic fenestration for macrocystic SC 12-14 cm). Diagnosis was established via magnetic resonance imaging and endoscopic ultrasound, with intra-cystic dosage of tumors markers (ACE and CA 19-9) in 2 patients. All patients were symptomatic and operated on 15-60 mo after diagnosis. Radiological evaluation showed constant cyst growth. Patients were informed about this new surgical modality that can avoid pancreatic resection. The mean operative time was 103 min (70-150 min) with one conversion. The post-operative course was marked by a grade A pancreatic fistula in one patient and was uneventful in the other two. The hospital stay was 3, 10, and 18 d, respectively. The diagnosis of macrocystic SC was histologically-confirmed in all cases. At the last followup (13-26 mo), all patients were symptom-free, and radiological evaluation showed complete disappearance of the cyst. Laparoscopic fenestration, as opposed to resection, should be considered for large symptomatic macrocystic SC avoiding pancreatic resection morbidity and mortality.