Heuristic algorithms strengthen researchers to solve more complex and combinatorial problems in a rea- sonable time. Markowitz’s Mean-Variance portfolio selection model is one of those aforesaid problems. Actually, Markowitz’s model is a nonlinear (quadratic) programming problem which has been solved by a variety of heuristic and non-heuristic techniques. In this paper a portfolio selection model which is based on Markowitz’s portfolio selection problem including three of the most important limitations is considered. The results can lead Markowitz’s model to a more practical one. Minimum transaction lots, cardinality constraints (both of which have been presented before in other researches) and market (sec- tor) capitalization (which is proposed in this research for the first time as a constraint for Markowitz model), are considered in extended model. No study has ever proposed and solved this expanded model. To solve this mixed-integer nonlinear programming (NP-Hard), a corresponding genetic algorithm (GA) is utilized. Computational study is performed in two main parts; first, verifying and validating proposed GA and second, studying the applicability of presented model using large scale problems.