Mesterolone is a synthetic androgenic-anabolic steroid (AAS) used for the cure of infertility and hypogonadism. Mesterolone cannot be analyzed using a UV detector because of the lack of a chromophore and this puts limitations on its direct UV analysis. This paper reports on the development and validation of a simple and cost-effective post-derivatized TLC-densitometric method using ceric sulfate as a staining reagent for the analysis of mesterolone and its degradation products under various stress conditions, as recommended in the ICH guidelines. The limit of detection and limit of quantification for mesterolone in this method were found to be 1.64 and 4.97 ng per spot respectively. The current study suggests that mesterolone is very prone to photochemical degradation, while quantum chemical calculations carried out as an integral part of this study supplement the assessed reactivity of mesterolone under applied stress conditions. The developed stability-indicating TLC-densitometric method can be employed for the analysis of mesterolone in the presence of its degradation products.