Background/Objectives: Basal cell carcinoma (BCC), the most prevalent form of human cancer, is traditionally treated by surgical and alternative destructive or topical chemical means, each with its advantages, challenges and drawbacks. We describe our experience treating BCCs with a topical concentrate of proteolytic enzymes enriched in bromelain (CPEEB) sourced from pineapple stems. CPEEB has strong proteolytic, antitumor-proapoptotic and inflammation modulation activities, and is approved for debridement of deep burns and starting phase 3 for chronic wounds. Methods: In the first proof of concept (POC) study (published), six BCCs on 3 individuals were treated with 5-6 daily CPEEB 10% topical applications under a Zinc Oxide based occlusive dressing for 9-12 hours each during a period of up to 10 days. These patients were followed for up to 4 years. In an additional 2 POC studies, 16 patients with one BCC each were treated every other day for a total of 7 applications of topical CPEEB 5% under a variety of occlusive dressings. The wounds were followed for up to 2 months before undergoing diagnostic excisional biopsy. Results: In the first study, clinical assessment of the BCCs and 2 excisional biopsies after 6 months suggested that all lesions were eradicated with spontaneous healing within ~2 weeks without clinical or histological recurrence for over 4 years. In the 2 subsequent studies, 16 histologically diagnosed superficial and nodular BCCs were treated using 4 application techniques. Excisional histology after 2 months confirmed BCC eradication in 7 of the patients. In 9 patients, with compromised occlusive dressings, histological eradication was incomplete. Treatment was well tolerated by all patients with the expected local skin reactions that completely healed within 2-3 weeks. Conclusions: Topical CPEEB 10% and 5% resulted complete eradication of the BCC when appropriately applied. CPEEB was well tolerated in all patients and all treated sites’ erosions healed without scars in <3 weeks. Further research is necessary to corroborate the results, refine the application technique and complete the regulatory process.