Background: Standardised therapeutic monitoring of field skin cancerisation is challenging. 5-fluorouracil (5-FU) is a common topical therapy for ultraviolet radiation (UV) and actinic keratosis (AK) but is often accompanied with adverse side effects. Monitoring of patients following treatment can be improved with novel imaging technologies.Objectives: This case series used new, improved facial imaging technology in assessing topical 5-FU treatment for actinic damage.Methods: A case series followed 18 participants treated with topical 5-FU over 2 weeks, with facial imaging at baseline, at the end of treatment and at Week 12 posttreatment. Skin characteristics were automatically measured across selected treatment areas using the VISIA three-dimensional (3D) multispectral facial imaging system.Results: VISIA analysis recorded sharp increases in erythema, UV-spots and skin roughness at Week 2 followed by reduction of erythema, UV-spots and skin roughness at 12 weeks posttreatment compared to baseline. Skin hyperand hypopigmentation was observed across treatment areas at Week 2 returning to baseline levels by Week 12. Participants demonstrated improved skin texture indicating smoother skin and significantly diminished UV-spots. Conclusions: 3D, multispectral facial imaging can facilitate topical treatment monitoring of field cancerisation. 5-FU treatment of field cancerisation as observed in VISIA images and data are consistent with clinical experience. 3D, multispectral imaging was efficient, noninvasive and objective in monitoring treatment of actinic damage, for example, by measurement of erythema as a surrogate marker for inflammation. For clinical trials of new treatment modalities for facial photodamage and field cancerisation, 3D multispectral imaging features new tools for analysis of skin characteristics, including