Advanced lymphedema is associated with a number of adverse skin changes including color, thickening of the epidermis, dryness, and hyperkeratosis. These changes are related to prolonged lymph stasis and contribute to an increased risk of infection. Similarly, lipedema is associated with skin thickening and appearance of nodular adipose deposition. Skin care is essential in both conditions. We examined whether inclusion of targeted skin products for 2 weeks to an established pre-surgical conservative treatment program was associated with beneficial effects on the skin condition in 150 patients with lymphedema and lipedema. Patients were randomly assigned to control or one of two treatment groups. All three groups (and for both lymphedema and lipedema) demonstrated a significant reduction in softness. Dimpling/ redness was significantly reduced in the targeted skin product groups for both patients with lymphedema or lipedema. Only patients with lipedema demonstrated a significant reduction in dryness/ hyperkeratosis following targeted skin product treatment. This study demonstrates that short-term use of targeted skin products in both patients with lymphedema and lipedema can be of benefit and further studies are needed to replicate these results and explore possible mechanisms.