Cryosurgery is an effective method for treatment of perianal gland adenoma (PAGA) and we had several successful treatments in our teaching hospital using this method. However, this article reports a failure of cryosurgical treatment of PAGA and severe complications in a dog suffering from hyper adrenocorticism."Pooh Pooh" was a nine year old intact male standard poodle taken to veterinary teaching hospital with signs of constipation and dyschezia. The owner reported a firm lump near by anus which bleeds occasionally. Clinical examination reveals an obese animal with slightly poor hair coat having a large multi focal and two smaller tumors around the anus. Biopsy was taken from lesions and after histopathology confirmation of PAGA, cryosurgery was done using a Liquid nitrogen spray apparatus and three freeze-thaw cycle performed on the lesions. Tissue temperature was monitored using Needle Thermocouples and Electronic Tissue Temperature Indicator. Classic sequences of cryo-lesions healing process were observed on follow up examinations during the first week. But in second week, abnormal exuberant granulation tissue, purulent discharge and soft tissue swelling were seen. Histopathology report for second biopsy specimen showed suppurative inflammation, exuberant granulation tissue and hepatoid texture of tumoral cells in several sites. After antimicrobial therapy the second cryosurgical operation was done but regrowth of abnormal exuberant granulation tissue and exacerbation of swelling and severe cellulitis were seen again. Review of the history and clinical findings led us to probable systemic disorders affecting wound repair process and Para clinic test results evidenced that "pooh pooh" is suffering from hyper adrenocorticism. The owner had no agreement with further tests and treatments and "pooh pooh" had put on sleep by his owner request. Three sequential phases (Rapid, Delayed and Immunological) are described for tissue cell death mechanism in cryosurgery. Laboratory animal studies have shown importance of immunological phase in tumors cryosurgery and some clinical reports have shown failure of cryosurgery in animals receiving exogenous corticosteroids, simultaneously. However, in this case, it seems endogenous corticosteroids not only had a negative effect on wound healing process but also affect the cryobiological behaviors of tumoral tissue exposing to cryogenic substance and led into failure of cryosurgical treatment.