Growth of economic systems depends on the development of their structural elements. Clusters are such structural elements in the context of economic analysis of a country at a meso-level, i.e., regional level. The goal of this study is to estimate the influence of regional cluster specialization on gross regional product (GRP). We have tested the hypotheses that there is a positive relationship between regional cluster specialization and GRP in the short and long term. In order to test these hypotheses, we have used the main theoretical and methodological aspects for cluster identification within the “top-down” approach. Firstly, we have discussed the practice of using the localization quotient (LQ) for cluster identification and shown various approaches for determining its cut-off value. After that, we have selected a method for analysis of regional cluster specialization, proposed by Lindquist, and adjusted it for the specifics of Russia’s economic structure. We have estimated the influence of cluster specialization on gross regional product. In order to assess regional cluster specialization, we have calculated the localization quotient, cluster size and cluster focus for 37 clusters in 80 regions of Russia during 2011–2015. We awarded a star to a cluster if the value of the localization quotient, cluster size» or focus exceeded their cut-off value. Further, we have summed up the stars for each cluster in a given region, in order to calculate cluster specialization of the region. Finally, we have conducted regression analysis and confirmed the hypotheses that there was a positive relationship between the level of cluster specialization and the GRP during 2011–2015. Consequently, we have confirmed the existence of positive agglomeration effects appearing as a result high level of cluster specialization of a region. These results and instruments may serve as reference points for development and rationalization of government cluster policy.