Background: Western blot (WB) is a standard technique used for detecting Dystrophin after gene correction therapies. This validated methodology shows good linearity, acceptable precision, and accuracy. Despite these characteristics, the results pose some intricacies due to the nature of the standard curve, the variability in the responses to treatment, and the fact that the results are compared to mdx mice which may express revertant fibers. The particular range of standard curve used for analysis can have a significant influence on the results. Objectives: To review the levels of expression detected by WB in the mdx mouse model and to discuss the complexities of the interpretation of the dystrophin quantification by WB. Approach: We analyzed 360 muscle samples, including; TA, EDL, Quadriceps, Heart and Diaphragm by WB in mdx mice (195) and BL10 wild type (166) that received vehicle treatment. The comparison was made between samples analyzed with different std curves – either broad range (0%-100%) or a narrow range of dystrophin (0%-40%). Results: mdx control samples showed levels of dystrophin between 0-3% when obtained from WB that included a std curve with a broad range (0-100%), and levels of 0-2.3% when analyzed with a narrower range (0%-40% dystrophin). Although the values obtained are similar, there is less variability in the data obtained with the lower range std curve. Discussion: The responses in the low-level range make it challenging to determine the ideal experimental design, stressing the importance of choosing the std curve according to the doses under investigation. The muscles of mdx mice sometimes show low levels of dystrophin, but the scientific community has not yet defined, “how little is too little”. We suggest that responses which overlap with the mdx levels of dystrophin should be evaluated in context with other functional tests.