Efforts at early detection of cancer have resulted in a sharp increase of overdiagnoses, ie, benign lesions being misinterpreted as malignant ones. Clinical overdiagnoses usually prompt a biopsy to be performed. The number of biopsies has risen dramatically, and the average time and diligence devoted to them have decreased. Biopsy specimens are often extremely small and sometimes crushed, leading to great difficulties in the assessment of histopathologic findings. In their fear not to overlook a malignant lesion, histopathologists confronted with an equivocal lesion tend to err on the malignant side, the results being histopathologic overdiagnoses and overtreatment. Epidemiologists have tried to counter those problems by cautioning against cancer screening and by inaugurating a change in nomenclature: the term “cancer” has been reserved for lesions likely to result in death, whereas earlier stages of the same process are referred to by different names emphasizing their ostensible innocuousness, and any diagnosis of a malignant neoplasm that does not produce symptoms or kill the patient is qualified as “overdiagnosis.” In contrast to those suggestions that ignore biologic entities and sacrifice the foundations of morphologic diagnosis, measures are discussed that may help to overcome the problem of overdiagnosis and overtreatment in more substantial fashion.