Introduction: Cryofrequency is a novel therapy which was developed with the combination of cold (cryotherapy) and heat (radiofrequency) application, causing a thermal shock effect on skin tissue. The thermal shock is believed to alter local metabolism. Objective: To investigate the effect of cryofrequency on the skin tissue of a mini pig in an in vitro and in vivo experimental model. Methodology: A small swine of the S. domesticus species, a male mini-pig (30 kg weight) was elected for the in vivo procedure subject. The in vitro step was performed on the extracted abdominal part of another subject of the same species and breed. Then, after the application of cryofrequency in the monopolar and bipolar form in vivo, a histological analysis was performed.Results: A higher temperature variation was observed comparing the pilot study in vitro with respect to the experimental one in vivo. Microscopically, an increase of collagen fibers and blood supply and decreased adipose tissue was observed after cryofrequency application. Conclusion: With the bipolar cryofrequency, no reduction of adipose tissue was observed, but regarding the connective tissue, extensive areas of collagen deposition were observed, as well as a great amount of new-formed collagen fibers.