The present study reports the clinical, histologic, and ultrastructural changes observed after the 6-month application of a novel skin cream containing a mixture of human growth factors and cytokines. Participants were asked to apply the human growth factor and cytokine skin cream twice daily to their entire face over a period of 6 months. A 3-mm punch biopsy was taken from the preauricular skin area before and after the treatment period. Further evaluations included photographic and clinical assessment of facial skin for wrinkles. After the treatment period, improved clinical appearance of periorbital and perioral wrinkles by 33% and 25% on average, respectively, was demonstrated. Histologic evaluation indicated moderate changes in the epidermal thickness as well as an increased fibroblast density in the superficial dermis at the end of the 6-month treatment period. Ultrastructural changes consistent with new collagen formation were shown by electron microscopy. This study, together with earlier studies, corroborates that topical application of growth factors and cytokines are beneficial in reducing signs of facial skin aging.