Combinational cryosurgery during daily imiquimod application ('immunocryosurgery') efficiently cures invading basal cell carcinoma (BCC). Since timing of the cryosurgery is considered crucial for effectiveness, our aim was to compare efficacy of two different timing schemes of the combination of cryosurgery and topical imiquimod: Cryosurgery (a) 2 weeks after (Arm I) vs (b) prior to the initiation of a 5 week daily imiquimod course (Arm II). 16 patients with 21 BCC were recruited in this prospective, randomized, open-label trial. 14 patients with 17 BCC were evaluated (Arm I: 7 patients/10 tumors vs Arm II: 7 patients/7 tumors) during scheduled interim analysis at 6 month follow-up (two patients dropped out, one non-compliant and one lost to follow up). The trial was revoked because study Arm I ('immunocryosurgery') was significantly superior to Arm II (adjuvant imiquimod) in achieving tumor clearance (10/10 vs 3/7 tumors; p=0.0147) and by overall treatment efficacy (9/10 vs 2/7 relapse-free tumors; p=0.0345). The same overall efficacy persisted after at least 18 months follow-up for those patients with tumor clearance after the trial treatment. The timing of cryosurgery during imiquimod application substantially determines the efficacy of this combinational approach in the treatment of BCC.