Objective: We treated two patients with recalcitrant lichen sclerosus (LS) of the penis with a combination of 1927 nm thulium fiber laser and methyl-aminolevulinate (MAL) photodynamic therapy (PDT)., Background Data: Therapy of LS is based on topical potent steroids, emollients, and topical calcineurin inhibitors. Circumcision is effective, but not always accepted. PDT represents a valid therapeutic option in refractory cases, but there are no reports about the association with 1927 nm thulium laser in the treatment of this pathology., Materials and Methods: We used to treat the affected areas with a combination of 1927 nm thulium fiber laser and MAL PDT in the same section. The same protocol was repeated after 1 month., Results: An improvement of lesions after the first treatment and complete cleaning after 3 months of therapy were noted. Results were maintained in the follow-up after 2 years., Conclusions: Association with 1927 nm thulium laser was able to amplify the effectiveness of PDT and to promote tissue remodeling. Despite the positive response to our case, clinical studies are lacking and further analysis could be performed on a wider population to better define correct dosage and safety profile. Further, it is necessary to compare this procedure with other treatments to establish the real effectiveness.