Photodynamic therapy (PDT) is an alternative to surgery for Bowen's disease. This monocentric retrospective study included 105 patients with Bowen's disease, treated with PDT between 2007 and 2013, who received a total of 151 different PDT fields. Comparison of immunocompromised and non-immunocompromised patients revealed that the former often had a previous history of squamous cell carcinoma (SCC; p = 0.004) and received more PDT fields (p = 0.007) than the latter. At least one SCC occurred post-PDT in 16 out of 105 patients in a PDT field. However, many of the patients were at risk of SCC and the possibility that the lesion did not have a mixed histology at baseline, but might simply be a transformation of non-PDT-responsive Bowen's disease, cannot be excluded. Although it is rare, patients should be closely monitored for SCC post-PDT.