DIP-STRs are compound markers formed by a deletion/insertion polymorphism linked to a microsatellite. They enable the deconvolution of unbalanced DNA mixtures from two individuals, up to 1000 fold excess of one contributor. In practice, this novel tool allows to test for the presence of a DNA of interest in traces appearing not useful because of the masking effect of the major DNA contributor. Thus far two sets of DIP-STRs have been published: the first set was described as proof-of-principle, while the second set was specifically developed for forensic applications. Here, we report on the first use of these markers in casework to show advantages and limitations in real examples. Traces, suggestive of containing unbalanced DNA mixtures (beyond standard STR mixture resolution), were selected from eight cases submitted to the Forensic Genetics Unit of the University Center of Legal Medicine of Lausanne-Geneva. Using 18 validated DIP-STRs, two to ten markers were selected for each case. A minor DNA contributor - undetected using conventional STRs - was detected for the trace samples of six cases. DIP-STR results contributed to each case, either by complementing Y-STRs results or by producing novel investigative leads. This was especially true with same sex unbalanced DNA mixtures, female minor/male major unbalanced DNA mixtures or when the source of the DNA mixture was said to come either from the suspect and the female complainant or from his brother and the female complainant. Interestingly, these markers were found to be more sensitive and specific than previously known. Positive results were obtained at 16,000-fold excess of major DNA using few picograms of input DNA, as well as from traces collected several months after the alleged offence. Likelihood ratios assigned to measure the strength of DIP-STRs' DNA evidence were modest (10), when accounted by only two DIP-STRs, and high (10(6)) when determined by six markers. In some cases the detection of extra alleles from additional minor DNA contributors or because of extremely unbalanced DNA ratios, limited the interpretation of the results. In conclusion, the DIP-STRs often provide additional value to the analysis of traces that cannot be exploited by the use of standard methods.