Background and purpose We hypothesized that upon sun exposure, a sub‐population of primary skin–derived mesenchymal‐like cells is deleteriously affected and thus contribute to the chronic inflammatory state in autosomal recessive variegate porphyria patients. The aim of this study was to isolate and characterize the mesenchymal‐like stem cells from different areas of the skin in a porphyria patient (sun exposed, SE, and sun protected, SP) and to compare them with cells from a healthy individual. Methods The proliferation rate and the migration ability of SE and SP cells were evaluated in the presence of an antioxidant compound, N‐acetylcysteine. A co‐culture of SE‐damaged cells with the conditioned medium from the enriched mesenchymal cell—like SP population was performed in order to regenerate the dermal injured tissue after sun exposure in patients. Results Results showed that the percentage of CD105+ cells varies between 3.9% in SP and 5% in SE of the healthy individual and between 3.6% and 1.4% in SP and SE in the porphyria patient, respectively. The osteogenic differentiation potential was lower in the porphyria patient when compared to the control. Furthermore, the expression of stem cell markers was more pronounced in SE than in SP cells of both control and porphyria. The use of N‐acetyl cysteine did not show any beneficial effects on porphyria SE cells. Treatment with SP‐conditioned medium slightly increased the expression of stem cell markers in SE of porphyria patient. Conclusion In conclusion, the pool of mesenchymal stem—like SE cells is affected in variegate porphyria patient along with modification of their self‐renewal and differentiation properties.