A 72-year-old man presented with actinic keratosis (AK) of the scalp confirmed by line-field confocal optical coherence tomography (LC-OCT) a novel non-invasive skin imaging technique. Patient was treated with Tirbanibulin 1% ointment once a day for 5 consecutive days and, after 8 days from baseline, mild erythema and desquamation was observed on the treated area, associated with mild pruritus. At the same time-point, L'LC-OCT revealed the presence of intraepidermal "targeted-like" cells, corresponding to apoptotic keratinocytes. After 2 months, clinical and instrumental examination showed the almost total disappearance of the AK. At the same time-point, a strong improvement of photoaging was noted at the level of the treated area. At 1-year follow-up, no relapse and/or new AK were observed. In conclusion, the reported case is emblematic of the short and long-term efficacy and safety of tirbanibulin in the treatment of AK, as already reported in the literature, as well as of the usefulness of non-invasive imaging technique such as LC-OCT in the therapeutic monitoring.