Background: As immunotherapy with checkpoint blockade becomes the backbone of melanoma treatment there is a need to better understand the biology associated with long term benefit. One particularly interesting set of patients are those with prolonged stable disease or response with residual findings on imaging. It is unknown if immunotherapy has led to scarring at the site of prior disease or if there are residual tumor cells being controlled by an ongoing immune response. Evaluating tissue from patients with prolonged responses provides a unique opportunity to determine the composition of residual lesions. Correlation with PET/CT helps determine if this is an accurate modality to reflect presence of residual viable tumor tissue. Methods: Metastatic melanoma patients that have attained long term stable disease after treatment with ipilimumab, nivolumab, or ipilimumab plus nivolumab were identified. Patients must have received ipilimumab, nivolumab or combination therapy 2+ years prior to enrollment and must have had stable disease for ≥ 6 months. Patients were consented and underwent PET/CT scans and biopsies of residual areas of stable disease. Pre- and post-treatment tissue samples underwent pathologic assessment to look at tumor cell content, fibrotic content, and inflammation. Results: Ten patients were consented for evaluation but only 7 met the screening criteria and underwent PET/CT and tissue biopsy. Six patients had FDG avid lesions on PET/CT which ranged in intensity from SUV 2.4-22. One patient had no FDG avidity in the areas of residual disease observed on CT. Biopsies from the residual stable lesions demonstrated predominantly necrosis and fibrosis with prominent pigment containing macrophages. One patient with an axillary nodal lesion with an SUV of 22 had active melanoma on pathology which was resected, and the patient has subsequently remained without progression of disease. Conclusions: Patients with durable stable disease after treatment with ipilimumab, nivolumab or ipilimumab and nivolumab combination therapy represent a unique population of melanoma patients treated with immune checkpoint inhibition. An examination of the residual lesions observed in these patients demonstrated predominantly necrosis and fibrosis consistent with resolving lesions. The presence of melanophages in these samples may suggest some ongoing immune surveillance. One patient did demonstrate residual melanoma suggesting the need for ongoing monitoring of this patient population.