- They're always on ground level. Don't bother scouring the walls and ceiling, they're always in places a character can walk to and pick up the speck of dust. 4 of the 5 characters you'll play as can pick up dust (the odd one out will be obvious) and it doesn't matter who collects them as long as they're picked up.
- Pick up specks of dust as soon as you see them. While you can often return to the previous screen and pick up one you missed; switching characters, coming back minutes later, etc. can cause the specks to move, and possibly disappear if you wait too long. So pick them up first!
- Just because you pick up a speck of dust in an area doesn't mean you won't find one there later. This only seems to happen when you're required to return to an area. I found all 75 on my first playthrough just by always keeping an eye out for specks of dust while playing through the game. That being said...
- They're not always out in the open. Scenery items in the foreground will often cover up part of the ground and if a speck of dust is on the ground there you may not be able to see it.
- Most areas/screens have at least one speck of dust. Check every area - especially when first arriving there - for a speck of dust, there probably is one. Same goes for all the rooms in the sewer. There's a ton of specks of dust down there.
- Finally, you can simply save, pick up a speck of dust, reload the save, and pick up the speck of dust again and have it count a second time. You can get all the way to 75 by picking up one speck 75 times, just by reloading your save repeatedly. You could also do this with a speck found closer to the end of the game to make up for ones you missed.