We tested the hypothesis that the genetic capability to mount an inflammatory response might contribute to the inter-individual variability of limbal stem cell graft (LSCG) outcome. Two functional polymorphisms in the IL-6 and TNF-alpha promoter regions were genotyped in 35 patients. A new score system (clinical assessment score, CAS) was set up in order to classify patients' clinical profile, and the main parameters relevant for LSCG as well as for the follow-up of the patients. Patients carrying at both loci a genotype associated with a lower production of both cytokines were classified as "low producers" (LP), while all the others were classified as "intermediate or high producers" (HP). LP patients did not show any difference in CAS before and after transplantation while a significant difference was present in HP patients. A similar trend was evident in the 35 months of follow-up. Polymorphisms of IL-6 and TNF-alpha can be used to identify subgroups of patients with higher risk of unsuccessful outcome.