INTRODUCTION: Neurofibromatosis is an autosomal-dominant systemic disease ranging from small skin nodules to deforming giant tumors. Surgical excision of neurofibromas (NF) is recommended for tissue diagnosis, to treat rapidly growing, symptomatic lesions, and to reduce risk of malignant transformation. Due to increased risk of uncontrollable hemorrhage from large vessels within the tumor, some giant NF are considered unresectable. The purpose of this study is to examine the surgical treatment of two giant NF which far exceed any reported in the literature. Previous reports of large NF have failed to reveal important vascular attributes which are unique to these tumors and their safe resection. METHODS: This study examined prior reports of large neurofibroma resections and a review of two cases of giant NF (>75kg) resected by the authors. Evaluations included CT, MRI, angiography and cardiac echography, in addition to physical and surgical findings, histology and long term follow-up. RESULTS: The two patients survived resection of unprecedented tumors without complication and enjoy normal lifestyles at two and five year respective follow-up. The surgical strategies of resection from normal periphery to central tumor in the deep fascial plane and controlled isolation of large tumor vessels were confirmed. A new description of the vascular pathology of NF is presented which may explain prior surgical failures. CONCLUSIONS: We report for the first time the successful resection of two giant tumors of NF, the surgical strategy developed for safe resection of similar tumors, and a previously unreported vascular pathology, characteristic of large neurofibromas. These findings may stimulate further investigation into the growth and surgery of "unresectable" tumors.