The increasing demand for product and process understanding as an active pursuit in the quality guideline Q8 and, more recently, on the draft guideline on quality and equivalence of topical products, has unveiled the tremendous potential of rheology methods as a tool for microstructure characterization of topical semisolid dosage forms. Accordingly, procedure standardization is a dire need. This work aimed at developing and validating a methodology tutorial for rheology analysis. A 1% hydrocortisone cream was used as model cream formulation. Through a risk assessment analysis, the impact of selected critical method variables (geometry, temperature and application mode) was estimated in a broad range of rheological critical analytical attributes-zero-shear viscosity, upper-shear thinning viscosity, lower-shear thinning viscosity, infinite-shear viscosity, rotational yield point, thixotropic relative area, linear viscoelastic region, oscillatory yield point, storage modulus, loss modulus, and loss tangent. The proposed validation of the approach included the rheometer qualification, followed by the validation of numerous operational critical parameters regarding a rheology profile acquisition. The thixotropic relative area, oscillatory yield point, flow point and viscosity related endpoints proved to be highly sensitive and discriminatory parameters. This rationale provided a standard framework for the development of a reliable and robust rheology profile acquisition.