Inclusion Criteria:

• Patients must have a diagnosis of NF1 based on NIH criterial with two or more of the following characteristics:

  • six or more cafe-au-lait macules (1.5cm or greater in size)
  • skin fold freckling in the axilla or groin
  • optic pathway glioma
  • two or more Lisch nodules of the iris
  • distinctive bony lesions such as dysplasia of the sphenoid wing or of a long bone such as the tibia
  • two or more neurofibromas of any type of 1 or more plexiform neurofibroma
  • first degree relative with NF1

• Participants must have at least four cutaneous neurofibromas on skin exam with the following qualities:

  • the lesion must be discrete by clinical exam and must not be contact with another skin tumor
  • the lesion must be amenable to measurement with calipers with minimum dimension of 5mm and maximum dimension of 30mm
  • the lesions must be located on the trunk, neck, or extremities (excluding the hands and feet) and must be located in an area that can be photographed
  • histologic confirmation of tumor type is not required in the setting of compatible clinical setting
• No treatment with an investigation agent for cutaneous neurofibromas within the last 3 months
• 18 years of age or older

Exclusion Criteria:

• Pregnant and nursing women
• Patients who have had chemotherapy or radiotherapy within 6 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 6 weeks earlier
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to imiquimod
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.