Whole-body bone scan is one of the most frequent diagnostic procedures in nuclear medicine. Especially, it plays a significant role in important procedures such as the diagnosis of osseous metastasis and evaluation of osseous tumor response to chemotherapy and radiation therapy. It can also be used to monitor the possibility of any recurrence of the tumor. However, it is a very time-consuming effort for radiologists to quantify subtle interval changes between successive whole-body bone scans because of many variations such as intensity, geometry, and morphology. In this paper, we present the most effective method of image enhancement based on histograms, which may assist radiologists in interpreting successive whole-body bone scans effectively. Forty-eight successive whole-body bone scans from 10 patients were obtained and evaluated using six methods of image enhancement based on histograms: histogram equalization, brightness-preserving bi-histogram equalization, contrast-limited adaptive histogram equalization, end-in search, histogram matching, and exact histogram matching (EHM). Comparison of the results of the different methods was made using three similarity measures peak signal-to-noise ratio, histogram intersection, and structural similarity. Image enhancement of successive bone scans using EHM showed the best results out of the six methods measured for all similarity measures. EHM is the best method of image enhancement based on histograms for diagnosing successive whole-body bone scans. The method for successive whole-body bone scans has the potential to greatly assist radiologists quantify interval changes more accurately and quickly by compensating for the variable nature of intensity information. Consequently, it can improve radiologists' diagnostic accuracy as well as reduce reading time for detecting interval changes.