Background: Cytology has always proudly been in forefront to absorb new technologic advances for practical use. The extensive and passionate implementation of digital imaging in telecytology, automated screening, education, training and certification, research, and publications is an appropriate example. Digitalization cytology records make its manipulation very simple. Several such manipulations, however, correspond to inappropriate changes and can affect final diagnosis of digital slides. Aim: To determine if global alterations of digital oral cytology images can affect its interpretation by an individual. Methodology: 20 digital images of cytological test smears of normal oral epithelium were acquired and stored in JPEG format. These slides were then manipulated restricted to global alterations (modify brightness, contrast and color levels, without focal changes) and were camouflaged from the original. A single power point presentation of 40 slides was created of group A (original) and group B (manipulated) digital slides, 20 each. This presentation was given to 5 experts for categorization on chart provided to them for easy data compilation. Intra-examiner pretest-post test difference was analysed using Wilcoxon rank sums test. Results: Out of the 5 examiners, diagnosis of three examiners changed significantly (p < 0.05) after slide alteration. Percentage of Over-interpretation ranged from 30-85% and under-interpretation 5-15% from unaltered slides for different examiners. Conclusion: Study clearly demonstrates that global manipulation of a digital image affects its interpretation and suggests that care needs to be taken when digital cytology images are used, to specifically ensure that their alteration does not affect diagnosis.