Objective: To define and classify the major types of intraocular lens (IOL) calcification. Design: Retrospective observational case series with clinicopathologic correlation. Participants: More than 400 IOLs explanted because of opacification. Methods: The authors reviewed the clinical information and histologic findings of all IOLs that had been explanted because of opacification or calcification of the IOLs accessioned in their laboratory between January 1999 and December 2004. Main Outcome Measure: The proposed mechanism that led to calcification of each IOL design. Results: Three major types of calcification were identified: (1) primary calcification, (2) secondary calcification, and (3) false-positive calcification or pseudocalcification. The primary form refers to calcification that is inherent in the IOL, that is, is based on possible inadequate formulation of the polymer, fabrication of the IOL, or issues with its packaging process. The calcification presumably occurs in otherwise normal eyes and generally is not associated with preexisting diseases. The secondary form refers to deposition of calcium onto the surface of the IOL most likely the result of environmental circumstances (e.g., changes in the aqueous milieu surrounding the implanted IOL associated with preexisting or concurrent diseases or indeed any condition that has disrupted the blood-aqueous barrier). By definition, it is not related to any problem with the IOL itself. The false-positive or pseudocalcification refers to those cases in which other pathology is mistaken for calcification or false-positive staining for calcium occurs. Conclusions: When evaluating the pathogenesis and nature of IOL calcification in or on any given design, one should categorize it according to these types. Primary calcification is IOL related and the IOL should be withdrawn or modified to correct the problem. After the cause is identified and the lens is implanted again, patients should be followed up for up to 2 years to be sure the problem is alleviated. Secondary calcification is by definition not IOL related; it may occur with virtually all IOL designs implanted under various adverse circumstances. No IOL, hydrophilic or hydrophobic, is immune to secondary calcification. The false-positive form is recognized readily in the laboratory and this erroneous diagnosis is avoided.