OBJECTIVE: To develop an algorithmic quantitative skin and subcutaneous tissue volume measurement protocol for lower extremity lymphedema (LEL) patients using computed tomography (CT), to verify the usefulness of the measurement techniques in LEL patients, and to observe the structural characteristics of subcutaneous tissue according to the progression of LEL in gynecologic cancer. METHODS: A program for algorithmic quantitative analysis of lower extremity CT scans has been developed to measure the skin and subcutaneous volume, muscle compartment volume, and the extent of the peculiar trabecular area with a honeycombed pattern. The CT venographies of 50 lower extremities from 25 subjects were reviewed in two groups (acute and chronic lymphedema). RESULTS: A significant increase in the total volume, subcutaneous volume, and extent of peculiar trabecular area with a honeycombed pattern except quantitative muscle volume was identified in the more-affected limb. The correlation of CT-based total volume and subcutaneous volume measurements with volumetry measurement was strong (correlation coefficient: 0.747 and 0.749, respectively). The larger extent of peculiar trabecular area with a honeycombed pattern in the subcutaneous tissue was identified in the more-affected limb of chronic lymphedema group. CONCLUSION: CT-based quantitative assessments could provide objective volume measurements and information about the structural characteristics of subcutaneous tissue in women with LEL following treatment for gynecologic cancer.