The patenting of ‘life’ forms - including human parts – raises a number of important issues that challenge the traditional understanding of intellectual property protection suggesting the need for institutional and policy reform. In Europe this debate has focused mainly on the EU Biotech Directive which has been incorporated into the European Patent Convention. In Europe, the vast majority of biotech inventions are essentially considered patentable on ethical grounds. However, the Court of Justice of the EU was called to decide on important issues raised by patenting of embryo stem cells in Brüstle and, more recently in International Stem Cell Corporation v Comptroller. The legal uncertainty generated by these contradictory decisions seems to be very similar to the current confusion created in the United States by the Supreme Court’s decisions in Mayo and Myriad. In order to mitigate the uncertainties coming from these decisions, the United States Patent and Trademark Office (USPTO) is working on a new guidance on subject matter eligibility. In particular, on the 16 of December 2014 the USPTO issued a new guidance describing an innovative eligibility test. The Guidance has the purpose of assisting USPTO staff in examination and post-grant proceedings to define whether claimed subject matter is eligible under 35 U.S.C. 101. Considering this overall framework, the paper has the aim to discuss and analyze this new guidance attempting to clarify the new rules for granting biotech patents.