Findings with uncertain clinical significance are frequently encountered on radiographs. A structure or opacity visible on radiographs could be due to several causes ranging from artifact or external structure to malignancy or a life-threatening process. The approach that a radiologist chooses to address ambiguous findings can have a significant impact on a patient's health. In this article we discuss the causes and impact of ambiguous findings on radiographs. We also discuss the various strategies radiologists can adopt to maximize clinical value and, when needed, reach a definite diagnosis.