We report on a 73-year-old male patient with granulomatosis with polyangiitis (Wegener's granulomatosis) who developed increasingly growing lesions of actinic keratosis (AK) and squamous cell carcinoma (SCC) of the scalp under systemic immunomodulatory therapy with azathioprine for more than 8 years. The patient underwent a first-line surgical therapy resulting in histologically confirmed R0 resection status followed by topical imiquimod treatment and cryotherapy. However, recurrence of AK/SCC progression could not be stopped sufficiently. Therefore, due to the difficult localization of the lesions at the head and the limitation of further surgical procedures, the patient was presented to our laser medicine department in order to consider complementary therapy options. The therapy approach was combining photodynamic therapy (PDT) with laser-assisted drug delivery (LADD). PDT has been successful in treating field cancerization for decades, but it has limitations in the treatment of hyperkeratotic lesions. Pre-treatment with LADD can be used to optimize the penetration depth of the prodrug 5-aminolevulinic acid (BF-200 ALA, Ameluz) and significantly increase the bioavailability as well as inducing an inflammatoric reaction. Following this therapeutic approach, we were able to achieve a stable disease over a follow-up period of 2 years after six sessions of combined LADD + PDT.