OBJECTIVE To review the rare clinical condition of venous gangrene of the extremities, particularly in association with malignant disease; to develop a treatment scheme for this difficult condition. DATA SOURCES Surgical articles on phlegmasia cerulea dolens, venous gangrene and other forms of noninfectious, nonarterial gangrene of the extremities from 1937 to the present were identified from published indexes and computer databases; experience with four additional cases treated by the authors is incorporated. STUDY SELECTION Studies selected for detailed review include those involved directly with venous gangrene and its investigation and treatment, and those relating to investigation of clinically similar conditions. DATA EXTRACTION Because of the rarity of venous gangrene, much of the available literature is descriptive, involves small numbers of cases and describes only limited experience with investigation and treatment; data extraction was done by a single reviewer. DATA SYNTHESIS Because of advances in diagnostic technology and thrombosis research, the assessment of suspected venous gangrene has changed significantly in recent years. Despite these advances, the prognosis for patients with this condition continues to be poor. The possible confounding roles of paradoxical reactions to anticoagulants and of primary hypercoagulable states are considered. CONCLUSIONS Objective demonstration of extensive thrombosis of the large veins of the involved extremity remains central to the diagnosis. The presence and stage of any associated malignant lesion must be rapidly determined to allow planning for further treatment. Because conventional anticoagulation frequently fails, it may be necessary to consider less well-established modes of therapy.