Dealing with uncertain risks is an important challenge. Uncertain risks need to be sharply distinguished from traditional, simple risks which can be calculated by means of statistics. Arguably current governance of uncertain risks tends to erode into organized irresponsibility, i.e., society's ill-preparedness and inability to deal with surprises, negative consequences and/or long-term impacts which are associated with uncertain risks, notwithstanding all institutions and procedures in place. In such cases, a particular pattern in risk regulation can be identified, the uncertainty paradox, which is an umbrella term for situations in which uncertainty is acknowledged, but the role of science is framed as one of providing certainty. This article highlights the need to further understand the uncertainty paradox by investigating actual decision-making processes. Through case-study research on EU GMO regulation this article examines how various actors actually deal with science, knowledge and uncertainty. Four mechanisms sustaining the uncertainty paradox are inferred: 1) uncertainty intolerance; 2) boundary work; 3) the inclination to equate uncertainty with risk; and 4) technocratic provisions. In conclusion, some suggestions are advanced as to how to break through the uncertainty paradox.