OBJECTIVES: We examined Ki-67 heterogeneity within single and between synchronous liver metastases of small intestine neuroendocrine tumors. METHODS: There were 27 patients (10 men and 17 women) with two or more liver metastases. The Ki-67 index was used to classify the tumors into World Health Organization grade 1, 2, or 3. The association between Ki-67 heterogeneity and tumor size of liver metastases was analyzed. Correlation of tumor grade with patient survival was also evaluated. RESULTS: Primary tumors from 20 patients were graded, including 17 grade 1 and three grade 2. A total of 188 liver metastases were resected, including 122 (65%) grade 1, 47 (25%) grade 2, and 19 (10%) grade 3. The highest tumor grade was grade 1 in 10 (37%), grade 2 in nine (33%), and grade 3 in eight (30%) patients. Patients with one or more grade 3 liver lesions had a shorter progression-free survival compared with those with grade 1/2 tumors (P textless .001). A positive association was found between tumor size and Ki-67 index (P = .04), as well as between tumor size and intratumoral Ki-67 heterogeneity (P textless .001). CONCLUSIONS: Intratumoral and intertumoral Ki-67 heterogeneity is common and positively correlated with tumor size. The presence of one or more grade 3 liver lesions predicts a worse prognosis.