Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer in the Caucasian population and its incidence is increasing worldwide. Although surgical procedures show a high cure rate with acceptable morbidity, non-surgical, pharmacotherapeutic approaches have been regarded as appropriate alternatives, and/or first-line treatments, in selected cases. Imiquimod (IQ) is a synthetic imidazoquinoline amine that locally enhances, through cytokine induction, both innate and acquired immune pathways, resulting in immunomodulating, antiviral and antitumor effects. Topical IQ 5% cream is approved by the FDA and the European Union for the treatment of small superficial BCCs (<2.0 cm); however, published data highlight the possibility of successful outcomes in larger lesions. We report three patients, each one presenting with a large BCC and successfully treated with IQ 5% cream. Although our cases and those from the literature do not rise to the level of evidence, IQ may be a reliable, efficacious and safe non-surgical option for selected cases of large superficial BCCs. Histological examination should occur at baseline and at the end of treatment along with clinical and dermatoscopic examination at least monthly during the course of the treatment and every 6 months for 2 years following the treatment.