The use of helium in plastic bag suffocation is a suicide method recently found in forensic cases. Although it is not common practice, there has been a strong increase in its use during the past 20 years, thanks to the accessibility of information on the web and materials needed to implement it. From a pathophysiological point of view, there are various theories on how helium can change the timing and, also, the cause of death when the head is inside a plastic bag. We report two cases where we believe that the action of helium, whose unequivocal use is demonstrated by the circumstantial data, has unfolded in a different way. In the first case, the discovery of an intense cyanosis of the face, blood leakage from the respiratory orifices and the destruction of numerous alveolar septa with histologically demonstrated blood extravasation, was left for a longer agonic period and a no negligible rate of pulmonary barotrauma in determination of death. In the second case, the total absence of external pathological phenomena, internal and histological, allows us to hypothesise an onset of death that is faster and catalysed by helium and explained by the known sympathetic hyperactivation and consequent cardiac arrhythmic death described in similar plastic bag suffocation cases.