The Story Goes On

There are a total of 50 unique items that you'll need to find, cumulatively, across all playthroughs. You can check your progress (aside from the achievement tracker, which actually works) in the main menu. Go to Stats, and at the top it will tell you how many unique items you've found. If you scroll down, you can see which items you've found as well, in case you have a bad memory and won't recognize new items when you see them.

Unfortunately, this achievement is entirely dependent on RNG. Every place where an item appears, it will always be a random item. So you will continually find new items early on, but as you get closer to the completion, you'll have to deal with more and more repeats before you find another new one. 

A few points to make:
 

• Never move on from a level until you've found the room with the yellow gem on your map. There is always one room per level with a random item sitting there for you to pick up. 
• Always search all rooms of a level, especially the top row of rooms, to check for an item shop. These shops sell three random items, so there's a much better chance of finding a new one there. 
• The movement speed up (brown boots), dash speed up (blue boots) and the two attack upgrades (speed and range) all count for this achievement. You'll almost unavoidably get many of the attack upgrades, but I had purposely ignored the blue boots since I found the dash to be pretty useless. Make sure you buy them each at least one. 
• Potions don't impact this achievement. 
• The wildcard has no impact on this achievement. 
• As you collect normal keys during each level, don't use them on normal chests. The normal chests almost exclusively contain health or money. Sometimes you'll come across gold chests. These have a chance to contain an item, so save your keys for gold chests. 

Those general tips will get you almost all of the items, but there are two unique ones:
 

• Lord Pecrtron can only be obtained in a specific way. Refer to Lord Pecrtron (25G) for details on how to obtain that item. 
• The White Hat can only be obtained from a specific character. As you're playing, during any level, in any room, there is a small chance for a character to appear. He'll be wearing a white hat and swinging his arms around. As soon as you enter the room and see him, dash towards him and hit him with your sword before he disappears. You'll be rewarded with the White Hat. This character is a random spawn, so be on the lookout. I encountered him numerous times during my time with the game, so you will have multiple chances to get his hat. 

Once you've gotten the two unique items and all other achievements in the game, you may still need a few more unique items. My strategy initially was to start from the harder levels, saving more items and hopefully finding rarer items, but this seemed to give the exact opposite result. Instead, when you're left with just hunting down unique items, I recommend you start each new cycle in the Forest. Even though you'll lose almost all of your items, it's the best way to find new ones. After around 10 cycles of the hardest levels, I found no new items, but then in two or three cycles starting from the Forest, I found the last four I needed. 

I haven't seen any information about this, but I suspect some items may be tied to some levels. This is just a theory of mine, but I never found the ice staff until I went through the Snow level again. Likewise with the Candy Corn and the Forest level. So if you take my advice above and start each new cycle from the Forest level, this won't be an issue. 

Lastly, regarding tracking which items you've found, there's really no need. Since there aren't any bad items (ones that negatively impact you or your stats), you'll be picking up every item anyway, whether it's a repeat or a new one. So don't worry about making a note of which ones you've found or which you still need. Continue through cycles of all levels and you'll eventually find them all. Unfortunately, that's the best advice I can give.