The value of alpha,beta-unsaturated ketones as key intermediates for the combinatorial assembly of four different templates on the solid phase, namely pyrimidines, dihydropyrimidinones, pyridines, and pyrazoles, was explored with individual syntheses of variably substituted model compounds. Starting from aldehydes grafted on polystyrene support, the Wittig and the Claisen-Schmidt reaction conditions were adapted to efficiently prepare alpha,beta-unsaturated ketones on the solid phase. Further derivatization of the alpha,beta-unsaturated ketones to form pyrimidines succeeded with a number of amidines. In a feasibility study, the potential to obtain, in a modular fashion, other small heterocycles from the same intermediates was assessed. In this solid-phase approach alpha,beta-unsaturated carbonyl intermediates can act as a three-carbon component and a primary enamine is utilized to complement the system for pyridine ring formation. Instead, with N-methylurea a dihydropyrimidinone is obtained. As an alternative, substituted hydrazines are incorporated in one orientation, providing pyrazoles with defined regioisomerism. The study indicates that alpha,beta-unsaturated ketones grafted on the solid phase can take a pivotal role as branching points in a number of synthetic diversity schemes and, therefore, represent versatile intermediates for the efficient preparation of combinatorial small molecule libraries.