Basal Cell Carcinoma Chemoprevention Trial

Inclusion Criteria:

* Veteran
* 2 (or more) qualifying basal cell carcinoma (BCC) lesions in the prior 5 years, with at least one located on the face, neck, ears, or scalp "Qualifying lesions are those that meet the two inclusion criterion bullet points below, and none of the exclusion criteria listed in "B"
* Qualifying lesions not in a field of prior radiation therapy
* Qualifying lesions not a recurrence after treatment, but the original lesion can qualify whether it recurred or not

Exclusion Criteria:

* Actinic Keratosis (AK) or Keratinocyte Carcinoma (KC) field therapy on the face (5-FU cream, imiquimod (IMQ), diclofenac gel, chemical peel, or photodynamic therapy) for BCC treatment on the face in the last 2 months because it can cause inflammation that may interfere with the imiquimod (IMQ) treatment. After 2 months, these patients can be included
* imiquimod (IMQ) therapy on the face in the past year, although such therapy in the more distant past is not an exclusion
* Suspicious skin lesions suggestive of any type of skin cancer present on the face at the initial exam conducted for the study must be removed and have another skin exam to confirm the facial skin cancer is cleared for 1 month prior to randomization so that the investigators can be confident that skin cancer lesions that arise during the trial are new
* Currently receiving or received in the past two months: immune checkpoint inhibitor, hedgehog pathway inhibitor, or oral capecitabine
* History of cutaneous T-cell lymphoma within the past year, but low-grade prostate cancer, patch stage CTCL, breast cancer, and history of solid hematologic cancer deemed to be in remission will be included
* Genetic disorder associated with very high basal cell skin cancer risk (i.e., basal cell nevus syndrome, xeroderma pigmentosum) because prevention efforts with imiquimod (IMQ) may have dramatically different efficacy in these patients compared to the general high-risk population
* Solid organ or bone marrow transplant recipient such as renal, hepatic, or cardiac transplant because these patients are at increased risk of KC (much greater risk of squamous cell carcinoma (SCC) than basal cell carcinoma (BCC)) and the associated immunodeficiency may affect the effectiveness of imiquimod (IMQ)
* Radiation therapy to the face
* Known allergy to IMQ or cream vehicle
* Woman currently pregnant or breast feeding
* Woman of childbearing potential unwilling to use birth control
* Judged by investigator to have a very high mortality risk within a year due to co-morbid illness
* Judged by investigator to be unlikely to comply with protocol requirements
* Judged by investigator not to be competent to provide informed consent
* Unable to communicate in English
* Enrolled in another therapeutic interventional trial