This study explores how the two different cellulosic ethanol system configurations (decentralized versus centralized) affect minimum ethanol selling price (MESP) and greenhouse gas (GHG) emissions. The eco-efficiency indicator, which simultaneously accounts for economic and environmental features, is also calculated. The centralized configuration offers better economic performances for small-scale biorefineries, while the decentralized configuration is economically superior for large-scale biorefineries. The MESP of the centralized configuration declines with increased biorefinery size up to a point and then rises due to the cost of trucking biomass to the biorefinery. In the decentralized configuration, railroad transport of pretreated and densified corn stover from depots to the biorefinery reduces GHG emissions compared to truck transport regardless of the biorefinery size. Decentralized processing also reduces MESP at larger biorefinery sizes if depots are located within about 14 km of rail service. Eco-efficiency analysis shows that that the centralized configuration is more sustainable for small-scale biorefineries. In contrast the decentralized configuration with railroad transport is more sustainable at large-scale biorefineries, and the MESP continues to decline with increasing biorefinery size.