For small and medium enterprises (SMEs) in the manufacturing industry, the ability to survive competition and run a profitable business depends on the performance of the manufacturing operation. Much industry work and many researchers have been applied to improve manufacturing operation performance; these efforts have resulted in structured procedures and methodologies such as Lean manufacturing, Total Quality Management, Total Quality Control, Agile manufacturing, Six Sigma and others. Each of these improvement methodologies has its own merits and shortcomings. Previous research projects addressed the idea of combining these methodologies in order to get a perfect combination that can solve all problems. One of those attempts is the integration of Lean and Six Sigma. All research work in this area has followed either a complementary or integrative approach. None of the research projects presented so far have followed a synergetic approach with mathematical modelling to integrate Lean and Six Sigma. Also, most of the Lean Six Sigma integration ventures have been in private manufacturing organisations. The literature has not provided a structured framework for deploying Lean Six Sigma in small and medium enterprises (SMEs). This research presents the Lean Six Sigma Framework (LSSF) for SMEs, which provides a different way of integrating Lean and Six Sigma using a synergetic approach based on mathematical modelling. The LSSF for SMEs defines operation variables and performance indicators. It provides operational mathematical models for controlling performance, a tools system for selecting the right tool for the problem, and performance targets, to ensure operation is performing at or above industry standard. The input to the LSSF development came from empirical study, observations, and feedback from computer simulation. The framework presents a step-by-step process to help with implementation and ensures the desired results are achieved. The LSSF was validated firstly through computer simulation and then through an industrial trial conducted at an SME manufacturer's premises