The goal of this work was to develop an objective, quantitative, and reproducible method of detecting fluorescence drift which may have occurred during DNA cell-cycle data acquisition. Quality control software, "TruPloid," is described that analyzes list-mode files to detect and quantify fluorescence drift using three separate statistical tests. We show that fluorescence drift may lead to a variety of measurement artifacts including high coefficients of variation, obscuring of small populations and creation of distinct artificial peaks. Forty percent of 50 archived list-mode files displayed fluorescence drift, which demonstrates the need for detection methods to deal with this source of DNA cell-cycle histogram artifacts.