Nucleolar protein PICT-1/GLTSCR2 (GLTSCR2) has both tumor suppressive and oncogenic activities, depending on the types of cancer tissue and its expression level. The role of GLTSCR2 in renal cell carcinoma (RCC) has not yet been addressed. The aims of this study were to evaluate GLTSCR2 expression in RCC tissue and to determine pathological significance of GLTSCR2 in terms of tumor grade. RCC and adjacent normal tissue from 84 different patients was retrieved from nephrectomy specimens. The expression level of GLTSCR2 in RCC tissues was determined via immunohistochemical staining and invasion was determined using transwell chambers with Matrigel-coated membranes. The expression of GLTSCR2 was suppressed in about 80% of the carcinoma specimens compared to noncancerous renal tissue and inversely correlated with Fuhrman nuclear grade (r=-0.40, p<0.05). Knockdown of GLTSCR2 expression increased the invasiveness of SNU267 RCC cells. The expression of GLTSCR2 was suppressed in RCCs and its downregulation accentuated the malignant phenotype.