For the estimation of grade and tonnage of the multiple-layer lignite deposits a sophisticated evaluation methodology, based on exploitation and quality parameters, is used. These parameters are usually determined empirically and the selected values are not always optimal. For the estimation of the optimal values, a new methodology based on response surface analysis is suggested. The minimum thicknesses for selective excavation of lignite and waste layers, as well as the maximum allowable ash of the mined lignite, were considered as the decisive control parameters, while the recovery of the lignite, the ash of the mined lignite, and the number of the exploitable lignite blocks were selected as the response variables. The developed methodology was applied in the South Field lignite mine in the area of Ptolemais. The estimated optimal values were compared to those currently applied and their impacts to deposit recovery, equipment utilization, and to the quality of the mined lignite were examined.