To determine whether an increase (or progression) in the degree of malignancy according to cytologic or histopathologic criteria corresponded with failure of intraocular melanoma control. Retrospective case control study from a single institution. Uveal melanoma patients had either fine- needle aspiration biopsy followed by irradiation and later enucleation or an eyewall resection followed by enucleation. The observation procedures were serial histology or cytopathology and histology, reanalyzed in a masked manner. The main outcome measures were change in the predominant tumor cell type, local tumor control, and metastases. There was not a significant correlation between a change in melanoma cell type and failure to control intraocular melanoma. Similarly, the latency between treatment and enucleation was actually less (but not statistically so) in tumors that showed no increase in melanoma malignancy cell type compared with those that had a more malignant cell type on serial examination. There was no correlation between a change to more a malignant cell type and local control failure in patients treated either with radiation or eyewall resection for uveal melanoma. To determine whether an increase (or progression) in the degree of malignancy according to cytologic or histopathologic criteria corresponded with failure of intraocular melanoma control. and later enucleation or an eyewall resection followed by enucleation. The observation procedures were serial histology or cytopathology and histology, reanalyzed in a masked manner. The main outcome measures were change in the predominant tumor cell type, local tumor control, and metastases. There was not a significant correlation between a change in melanoma cell type and failure to control intraocular melanoma. had a more malignant cell type on serial examinati on. There was no correlation between a change to more a malignant cell type and local control failure in patients treated either with radiation or eyewall resection for uveal melanoma.