The introduction of numerous immunotherapeutic agents into the clinical arena has allowed the long time promise of immunotherapy to begin to become reality. Intralesional immunotherapy has demonstrated activity in multiple tumor types, and as the number of locally applicable agents has increased, so has the opportunity for therapeutic combinations. Both intralesional Bacillus Calmette-Guerin (ILBCG) and topical 5% imiquimod cream have been employed as single agents for the treatment of dermal/subcutaneous lymphatic metastases or in-transit melanoma, but the combination has not previously been reported. We used this combination regimen in nine patients during the period from 2004-2011 and report their outcomes here. All patients were initially treated with ILBCG, followed by topical imiquimod after development of an inflammatory response to BCG. In this retrospective study, we examined their demographics, tumor characteristics, clinical and pathologic response to treatment, associated morbidities, local and distant recurrence, and overall survival. The 9 patients (8 male) had a mean age of 72 years (range 56 - 95). Mild, primarily local toxicities were noted. Five patients (56%) had complete regression of their in-transit disease and one had a partial response. The three others had “surgical” complete responses with resection of solitary resistant lesions. The mean interval between the first treatment and complete resolution of in-transit disease was of 6.5 months (range 2 – 12). With a mean follow-up of 35 months (range 12 – 58), seven patients (78%) had not developed recurrent in-transit disease. Two patients (22%) have died of non-melanoma causes, and none have died due to melanoma.